bims-enlima Biomed News
on Engineered living materials
Issue of 2026–06–14
75 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool
  1. Packed Hydrogel Microfibers as Scaffolds Supporting Dynamic Cellular Behavior and Biomaterial Inks in 3D Printing.
  2. Author Correction: De novo design of quasisymmetric two-component protein cages.
  3. Influence of protein aggregates, extracellular vesicles, and lipoprotein fusion on ionizable lipid nanoparticles protein corona analysis.
  4. From Light to Life: Molecular Mechanisms and Macroscopic Transformations in Photoresponsive Hydrogels.
  5. Enhanced integrin-mediated adhesion and proliferation of Schwann cells using highly aligned, dual-functional fibrous scaffolds.
  6. Development of a Laminin-511 Inspired 3D Zwitterionic Hydrogel for Human Pluripotent Stem Cell Culture.
  7. Bottom-Up Synthesis and Active Assembly of DNA Networks by Biomolecular Nanomachines.
  8. Isotropic shrinkage of patterned vacancies enables three-dimensional nanoprecise metastructures for visible light applications.
  9. Ordered nanoplastic-elastomer networks resolve conflict between softness and stability.
  10. Nanofluidics for Pioneering Synthetic Biology of Bottom-Up Cell-Free Molecular Systems.
  11. Architecting bioinspired nanocrystalline domains for ultimate robust and transparent cellulose photonic hydrogels.
  12. Overprinting with tomographic volumetric additive manufacturing.
  13. Generative design of programmable asymmetric β-barrel nanopores.
  14. Engineering Dynamic Hydrophobic Domains in Bioreinforced Ionic Hydrogels for Robust and Transparent Soft Electronics.
  15. Highly Conductive and Durable MXene/CNC/PEDOT:PSS-PNIPAm Hydrogel for Bioinspired Self-Sensing Soft Actuators.
  16. Physics-guided design of intrinsically disordered proteins.
  17. A biomineralized light-guiding structure in the porous calcitic skeleton of the sea star Protoreaster nodosus.
  18. Artificial morphogenesis of curved surface structures inspired by differential growth in biology.
  19. Soft Hardware, Flowing Software: Reconfigurable Microfluidics for Adaptable Chemical Computation.
  20. MARBL: A Live-Cell Method for Profiling Bioenergetic Heterogeneity by Noncanonical Methionine Labeling of the Cell Surface Proteome.
  21. Sticky enzymes: increased metabolic efficiency via substrate-dependent enzyme clustering.
  22. Comprehensive mechanical reinforcement of hydrogels via network refinement.
  23. High-Resolution 3D Bioprinted Hydrogel Scaffolds Enable Sustained Intraperitoneal Cell Delivery.
  24. Cellulosic Hydrogels Comprising Cellulose Nanocrystals or Chitin Nanocrystals for Historic Ceramic Conservation.
  25. Loach-Inspired Lubricant and Antibacterial Hydrogels with Thermochromism for Multifunctional Coatings.
  26. Alginate-Coated Collagen Hydrogel Tubes for Scalable Cell and Biotherapeutic Particle Manufacturing.
  27. Nonlinear rheology of laminin-111-modified hyaluronan hydrogels.
  28. Protocol for synthesis and mechanical characterization of polyacrylamide hydrogels of varying stiffness for cell culture applications.
  29. Synthetically designed anti-defense proteins overcome barriers to bacterial transformation and phage infection.
  30. Bio-Inspired and Protein-Based Elastomeric Materials.
  31. Hierarchical laser-programmed soft actuators for designing bionic robots with freeform morphing shapes.
  32. Multi-scale structural engineering enables ultra-strong and tough eutectogels.
  33. Layer-by-layer shear densification for multiscale hierarchical alignment in bulk hydrogels.
  34. Target-triggered assembly of engineered bacteria enables dual-mode detection of microRNA.
  35. Generic optimization procedure for high-resolution printing by stereolithography of 3D scaffolds compatible for cell culture applied to a small intestinal architecture.
  36. Programmable DNA hydrogels for dual-mode PD-L1 suppression via polyvalent LYTAC mimics and transcriptional silencing.
  37. A Methodological Approach to Relate Pentapeptide Sequence, Atomistic Self-Assembly, and Gelation Behavior.
  38. Nanodroplet-Confined Electroplating Enables Submicron Printing of Metals and Oxide Ceramics.
  39. Advancing mechanobiology from single molecules to complex cellular systems.
  40. Bioinspired Real-Time Dynamic Responsive Structural Colors.
  41. Domain Coordination Governs Pore Architecture in Transient Double-Network Antibody-Binding Polyprotein Hydrogels.
  42. From Colloids to Hydrogels: Concentration-Dependent Cytocompatibility of Carboxylated Cellulose Nanocrystals Prepared via Deep Eutectic Solvents.
  43. Beyond Molecular Determinism: State-Convergent Polymerization as a Functional Design Principle Under Chemical Complexity.
  44. SPACE-seq integrates spatial transcriptomics and lineage tracing in native tissues.
  45. SciPhy: A Bayesian phylogenetic framework using sequential genetic lineage tracing data.
  46. A Single-Cell Bioprinting Method to Reconstruct Native Cellular Microenvironments with Subcellular Resolution.
  47. Robust analytical methods for bis(monoacylglycero)phosphate profiling in health and disease.
  48. Synthesis of bundle copolymers as an emergent class of copolymer architecture.
  49. Enhancing small-molecule-mediated translational control through multivalent RNA aptamers.
  50. BioPrinted Hearts.
  51. Optimized cumate toolkit for tunable protein expression during in vitro and in vivo studies of Burkholderia cenocepacia.
  52. Scalable hierarchical textile fibers toward personalized wearable atmospheric water harvesting.
  53. Stepwise multi-gate control of the HOG MAPK pathway under hyperosmotic stress.
  54. Tet Trim-Away: A conditional rapid protein degradation system for Tetrahymena thermophila.
  55. Peptide-MHC-targeted engineered virus-like particles enable selective priming and gene editing of tumor-specific T cells.
  56. Synthesis and applications of 1D and 2D nanoparticles prepared through crystallisation-driven self-assembly.
  57. A nanoscale Jitterbug transformer from DNA.
  58. Spatially resolved m6A profiling using m6A-ARTR-DBiT.
  59. Total Synthesis of Conjugation-Ready Sulfated Red Algae Carrageenan Oligosaccharides for Sensing Applications.
  60. Programmable MOF-CNC Nanohybrid Networks Enabling Ion Transport Sensing and Efficient Water Purification.
  61. Sustainable functionalization of natural polysaccharides via multicomponent reactions: Designs, properties, and applications.
  62. High Entanglement in Hydrogels: From Polymer Physics to Robust Mechanics.
  63. 3D printed trichome-inspired permeable bioadhesive for wearable bioelectronics.
  64. Tunable and Orthogonal ECF and Anti-σ Threshold Gates for Temporal Control of Heterologous Gene Expression.
  65. Scalable Conformal Electronics Based on Roll-to-Roll Exfoliated van der Waals Semiconductors.
  66. Inverted Potentials Enhance Electron Bifurcation Efficiency Prior to Steady State.
  67. A digital droplet microarray for measuring tolerance to antibiotics.
  68. Searching for sequence features that control DNA cyclizability.
  69. Programmable Nanoarchitectonics for Artificial Cells via Coupled Multidimensional Regulation of Phase State and Multiscale Transport Dynamics.
  70. Grafting polymer brushes from nylon surfaces via hydrogen atom transfer.
  71. Engineering human PEG10-based nanoparticles for RNA self-packaging, delivery and cancer therapy.
  72. Label-Free and In Situ Glycophenotyping Using a Glycocalyx-Mimetic Electrochemical Transducer.
  73. Cell size modulates ferroptosis susceptibility.
  74. Apical-out polarity in epithelial spheroids requires α6β4 integrins, cell proliferation, and anchorage-independence.
  75. On the Distribution of Free-Energy in Metabolism.
  1. Adv Healthc Mater. 2026 Jun 06. e03969
    Packed Hydrogel Microfibers as Scaffolds Supporting Dynamic Cellular Behavior and Biomaterial Inks in 3D Printing.
    M Gregory Grewal, Remington M Martinez, Georgia T Helein, Montserrath G Ibarra Rivera, Rodolfo Martinez, Jenna L Sumey, Steven R Caliari, Christopher B Highley.
      Particle-based hydrogels have been used as injectable scaffolds, biomaterial inks for extrusion bioprinting, and permissive systems for 3D cell culture owing to their unique physical properties, including bulk yielding and porosity. These properties are in part governed by interparticle interactions and spatial organization, with limited potential to design these properties in systems based on spherical hydrogel microparticles. Here, we engineer particle-based hydrogels where each particle is a discrete electrospun hydrogel microfiber that has been segmented to a length of 93 ± 51 µm, with a diameter of 1.6 ± 0.3 µm, presenting unique viscoelastic properties allowing stability without interparticle crosslinking (annealing). The fibers' flexibility and high aspect ratios enable interactions among fibers that give packed hydrogel microfiber (PHM) materials that are mechanically robust, can stretch without breaking when strained, and exhibit tissue-mimetic stress relaxation under constant strain. As cell culture scaffolds, shear-induced alignment of the individual fibers within 3D printed PHM filaments provide topographical cues to cells that promote alignment. Cells embedded in 3D within PHMs spread due to the permissive microenvironment presented by the microfibers. This work highlights strengths of fiber-based particle systems as dynamic and permissive scaffolds and printable biomaterials for tissue engineering and regenerative medicine.
    Keywords:  bioprinting; granular hydrogels; hydrogels; microfibers; viscoelasticity
    DOI:  https://doi.org/10.1002/adhm.202503969
  2. Nature. 2026 Jun 09.
    Author Correction: De novo design of quasisymmetric two-component protein cages.
    Shunzhi Wang, Ying Xie, David Chmielewski, Connor Weidle, Tong Shu, Green Ahn, Ryan D Kibler, Cindy Hernandez, Wei Chen, David Camilo Duran, Ann Carr, Asim K Bera, Sangmin Lee, Justin Decarreau, Alex Kang, Evans Brackenbrough, Emily Joyce, Kejia Wu, Andrew J Borst, Andrew Favor, Buwei Huang, Frank DiMaio, Liam J Holt, David Baker.
      
    DOI:  https://doi.org/10.1038/s41586-026-10763-6
  3. Nat Commun. 2026 Jun 12. pii: 5261. [Epub ahead of print]17(1):
    Influence of protein aggregates, extracellular vesicles, and lipoprotein fusion on ionizable lipid nanoparticles protein corona analysis.
    Babak Borhan, Amanda M Murray, Amir Ata Saei, Bahareh Ghaffari, James E Jackson, Naseeha Mohammed, Michael J Mitchell, Hojatollah Vali, Kathryn A Whitehead, Morteza Mahmoudi.
      Since 2018, ionizable lipid nanoparticles (LNPs) have revolutionized nucleic acid therapeutics. However, achieving potent extrahepatic delivery remains a formidable challenge, primarily due to rapid hepatic uptake driven by apolipoprotein adsorption. While analyzing the LNP protein corona is essential for engineering organ-specific tropism, these soft materials present unique analytical hurdles. Co-isolation of blood-borne contaminants, such as extracellular vesicles and lipoproteins, often masks the true corona composition. This perspective examines the critical need for refined proteomic strategies to distinguish genuine corona proteins from impurities. We propose tailored investigative approaches, suggesting the LNP protein corona significantly differs from the rigid shells observed on inorganic nanoparticles.
    DOI:  https://doi.org/10.1038/s41467-026-74240-4
  4. Polym Sci Technol. 2025 Dec 23. 1(10): 812-831
    From Light to Life: Molecular Mechanisms and Macroscopic Transformations in Photoresponsive Hydrogels.
    Peng Guo, Liang Dong, Bin Xue, Yi Cao, Jiapeng Yang.
      Photoresponsive hydrogels are dynamic polymeric networks capable of undergoing spatiotemporally controlled changes when exposed to light stimuli. Their capacity to translate photon-triggered chemical reactions into macroscopic property changes enables diverse applications in tissue engineering, drug delivery, soft robotics, and dynamic cell culture. This review focuses on the fundamental question of how light-induced molecular events are transduced into macroscopic transformations in hydrogel properties. We classify these materials by their core photochemical mechanisms: photo-triggered bond formation, bond cleavage, conformational change, and photoinitiated polymerization. Such processes modulate the network structure via crosslink formation, altered crosslinking density, or light-triggered supramolecular self-assembly. Special attention is given to protein-based systems, which offer distinct advantages such as reversible conformational switching, genetic encodability and biocompatibility. By elucidating the engineering principles that connect photochemistry to bulk behavior, this review surveys emerging biomedical and engineering applications and provides a framework for the rational design of next-generation photoresponsive hydrogels.
    Keywords:  biomedical applications; dynamic mechanical property; light stimuli; macroscopic change; photochemistry; photoresponsive hydrogel; photoresponsive protein; polymeric network
    DOI:  https://doi.org/10.1021/polymscitech.5c00102
  5. NPJ Soft Matter. 2026 ;2(1): 14
    Enhanced integrin-mediated adhesion and proliferation of Schwann cells using highly aligned, dual-functional fibrous scaffolds.
    Yin Mei Chan, Nicola G Judge, Rebecca K Willits, Matthew L Becker.
      Developing biomaterials that combine tunable mechanical properties with precise biochemical functionalization is critical for advancing peripheral nerve regeneration. Here, we report the synthesis and characterization of a novel family of allyl-containing semi-aromatic polycaprolactone copolymers, synthesized via a one-pot ring-opening copolymerization. By varying monomer composition, copolymers possessing a range of thermal and mechanical properties were obtained. Aligned fiber scaffolds were fabricated by touch-spinning and functionalized with bioactive peptides RGD and YIGSR via strain-promoted azide-alkyne cycloaddition and thiol-ene click chemistries, yielding dual-functionalized fiber scaffolds with spatiotemporal control of functionalization densities. Schwann cell cultures revealed enhanced 67 kDa laminin receptor activity on YIGSR-functionalized scaffolds and significantly increased proliferation on softer materials decorated with peptides, demonstrating the synergistic influence of matrix mechanics and bioactive cues. This modular platform offers tunable scaffold properties and controlled biochemical functionalization to elicit favorable Schwann cell responses, providing a promising strategy for next-generation nerve regeneration materials.
    Keywords:  Biotechnology; Chemistry; Materials science
    DOI:  https://doi.org/10.1038/s44431-026-00028-7
  6. ACS Appl Mater Interfaces. 2026 Jun 11.
    Development of a Laminin-511 Inspired 3D Zwitterionic Hydrogel for Human Pluripotent Stem Cell Culture.
    Erica K Wagner, Di Liu, Amy D Laflin, Shaili Lakhotia, Kangxuan Rong, Srishti Khetan, Haoxuan He, Joel Gutierrez Estupinan, Ronit K Kumar, Chenjue Tang, Shuibing Chen, Shaoyi Jiang.
      Human pluripotent stem cells (hPSCs) hold enormous potential for regenerative medicine and disease modeling applications. These cells, however, are commonly cultured on Matrigel, a 2D coating of mouse origin and significant complexity, hindering their clinical translation. These issues have motivated the development of (a) 2D natural alternatives, which can mimic the extracellular matrix niche, but result in cytoskeletal and epigenetic changes, insufficient cell-cell and cell-matrix interactions, lineage biases upon differentiation, and challenges with scale-up due to surface area constraints and (b) 3D synthetic alternatives, which can be xenogeneic-free but are afflicted with spontaneous differentiations, incompatibility with common media, and a lack of receptor-specific ligands. To overcome these limitations, we developed a fully synthetic, chemically defined, xenogeneic-free, highly biocompatible, ligand-incorporated, and cell-mediated degradable 3D culture system. We demonstrated a zwitterionic polycarboxybetaine (PCB) hydrogel inspired by laminin-511 in the early embryonic niche (PCB-LN511) can outperform other commercial substrates such as Matrigel and iMatrix-511, and we successfully performed 10 passages over 40 days, maintaining excellent pluripotency expression and retaining differentiation capabilities. The resulting PCB-LN511 provides a synthetic alternative to Matrigel for 3D hPSC culture, overcoming the current limitations with both 2D natural and 3D synthetic alternatives for stem cell culture.
    Keywords:  3D cell culture; biomaterials; engineering microenvironment, and biomimetic materials; human pluripotent stem cells; stem cell niche; zwitterionic hydrogel
    DOI:  https://doi.org/10.1021/acsami.6c05771
  7. Small. 2026 Jun 11. e14262
    Bottom-Up Synthesis and Active Assembly of DNA Networks by Biomolecular Nanomachines.
    Farhana Afroze, Richard J Archer, Mahammad Mustakim, Rakesh Das, Arif Md Rashedul Kabir, Yuuto Miura, Rubaya Rashid, Kazuki Sada, Tetsuya Hiraiwa, Shin-Ichiro M Nomura, Shogo Hamada, Akira Kakugo.
      Active assembly of matter is a defining trait of living systems, enabling the creation of far-from-equilibrium materials essential for the functionality of life. This is achieved through energy-dissipative, multi-step processes facilitated by biomolecular nanomachines performing bottom-up chemical and mechanical assembly of matter. Mimicking such active assembly synthetically remains a challenge. Here, a bio-inspired bottom-up strategy for energy-dissipative material assembly, driven by biomolecular nanomachines and overcoming thermodynamic and diffusive constraints, is demonstrated. Specifically, two chemically-fueled biomolecular nanomachines-DNA polymerase and kinesin-are used to demonstrate a multi-step chemical synthesis and mechanical manipulation process. This results in a DNA biopolymer network with complex hierarchical morphologies unattainable by self-assembly alone. DNA polymerase generates DNA, which forms a fibrous 2D-network when actively connected and pulled between kinesin-powered motile microtubules. Experimental data and simulations show that both DNA-DNA interactions and active mechanical forces from molecular motors are essential to this process. Furthermore, key factors for network formation are investigated by systematically investigating DNA polymerase incubation time and microtubule density. The present work provides a key step toward bottom-up fabrication of complex and dynamic materials by mimicking the sophisticated assembly strategies of living systems, potentially providing a framework for future materials assembled by nanomachines.
    Keywords:  DNA; active assembly; biomolecular; bottom‐up fabrication; energy‐dissipative assembly; nanomachines
    DOI:  https://doi.org/10.1002/smll.202514262
  8. Nat Photonics. 2026 ;20(6): 653-663
    Isotropic shrinkage of patterned vacancies enables three-dimensional nanoprecise metastructures for visible light applications.
    Quansan Yang, Gaojie Yang, Takahiro Nambara, Hiroyuki Kusaka, Yuichiro Kunai, Alex C Matlock, Corban Swain, Brett Pryor, Yannick Salamin, Daniel Oran, Hasindu Kariyawasam, Ramith Hettiarachchi, Dushan Wadduwage, Marin Soljačić, Peter T C So, Edward S Boyden.
      Three-dimensional metastructures with nanoscale feature sizes exhibit unique properties compared with structures with larger feature sizes, but are difficult to fabricate. Here we introduce implosion carving (ImpCarv), a method for photopatterning vacancies of complex geometry throughout materials, followed by isotropic shrinkage (>10-fold). ImpCarv works by photoactivating sensitizers to generate reactive oxygen species that cleave a swollen hydrogel at defined points, followed by controlled shrinkage via dehydration. ImpCarv creates three-dimensional metastructures where the refractive index of each point throughout a material can be specified with nanoscale precision via material presence or absence. By leveraging refractive index programmability for precise phase control, we demonstrate an all-optical machine learning device with nanoscale neuron sizes operating at visible wavelengths. ImpCarv may thus support diverse applications in nanophotonics and nanotechnology.
    Keywords:  Materials for optics; Nanoscience and technology; Optical materials and structures
    DOI:  https://doi.org/10.1038/s41566-026-01896-1
  9. Nat Commun. 2026 Jun 10.
    Ordered nanoplastic-elastomer networks resolve conflict between softness and stability.
    Yan Wang, Zhangkan Lin, Zheqi Chen, Guodong Nian, Shaoxing Qu, Yingwu Luo.
      Soft materials often fail through snap-through instability, where a small increase in load causes a sudden, catastrophic deformation. However, overcoming this instability requires a polymer network of two seemingly contradictory behaviors: softness at small strains to allow deformation, but early stiffening at afterward strains to prevent instability. Here we resolve this conflict by designing an architecture of ordered nanoplastic-elastomer network. We identify two design principles: a small volume fraction of rigid plastic nanodomains is orderly arranged within a soft elastomer matrix; the nanodomains and matrix are strongly linked by covalent bonds. These features together produce a crucial effect: macroscale strain is greatly amplified at the microscale, inducing earlier stiffening while retaining small-strain softness. Theoretically and experimentally, we demonstrate that this network architecture can prevent notorious premature failure in dielectric elastomer actuators, and greatly enhance the actuation performance. These results suggest a general route to design soft materials that resist catastrophic instability-induced failure.
    DOI:  https://doi.org/10.1038/s41467-026-73807-5
  10. ACS Synth Biol. 2026 Jun 12.
    Nanofluidics for Pioneering Synthetic Biology of Bottom-Up Cell-Free Molecular Systems.
    Shiming Wu, Qun Ma, Madoka Takai, Yan Xu.
      Synthetic biology via bottom-up assembly is transitioning from stochastic, extract-based cell-free systems toward reconstituted, molecularly defined cell-free molecular systems. Transitioning to molecularly defined systems provides a path to quantitative design; however, the active assembly of these molecular building blocks into ordered spatiotemporal architectures remains a formidable challenge in synthetic biology. In this perspective, we propose nanofluidics as a transformative platform to bridge this gap. By leveraging nanoconfinement effects and precision mass transport, nanofluidics facilitates the active assembly of molecular building blocks into functionally integrated spatiotemporal structures, thereby pioneering the synthetic biology of bottom-up cell-free molecular systems. Specifically, we discuss how nanofluidics enables precise control over fluid dynamics and single-molecule behavior within nanochannels and facilitates molecular active-assembly and tunable interactions of molecular components by engineering design of nanofluidic devices. Furthermore, we highlight key challenges and opportunities using nanofluidics to build next-generation cell-free molecular systems with single-molecule resolution. This perspective provides a strategic roadmap for the synthetic biology of bottom-up cell-free molecular systems.
    DOI:  https://doi.org/10.1021/acssynbio.6c00178
  11. Sci Adv. 2026 Jun 12. 12(24): eaed8263
    Architecting bioinspired nanocrystalline domains for ultimate robust and transparent cellulose photonic hydrogels.
    Qiongya Li, Chenchen He, Wenxin Zhang, Yuyu Zhang, Jinhao Huang, Kuoxi Xu, Fusheng Zhang, Guangyan Qing.
      Biomimetic spider silk achieves remarkable functionalities through hierarchical architectures with highly oriented crystalline domains, offering potential across multiple disciplines. However, achieving uniform alignment and spatial control of nanocrystalline domains remains a critical challenge, limiting the realization of structure-derived optical and mechanical functionalities in bioinspired systems. Here, we develop an ultrastrong, transparent photonic hydrogel composed of cellulose nanocrystals (CNCs), wherein a programmable five-stage stretching-pause process enables precise alignment of CNC domains without sacrificing their intrinsic chirality-unattainable in conventional flexible polymers. This strategy facilitates uniform nanocrystal reorientation (orientation factor = 0.91) and transforms the porous network into aligned nanofibril bundles, yielding optical transparency (>90%) with anisotropic polarization responses, superior mechanical strength (61.6 MPa), toughness (251.8 MJ·m-3), and fatigue resistance (226.7 kJ·m-2). The flexible hydrogel resists creasing and serves as a sustainable scattering polarizer for programmable polarized displays and secure information encryption, providing a versatile platform for advanced optical and electronic applications.
    DOI:  https://doi.org/10.1126/sciadv.aed8263
  12. Nat Commun. 2026 Jun 08.
    Overprinting with tomographic volumetric additive manufacturing.
    Felix Wechsler, Viola Sgarminato, Riccardo Rizzo, Baptiste Nicolet, Wenzel Jakob, Christophe Moser.
      Tomographic Volumetric Additive Manufacturing (TVAM) is a light-based 3D printing technique capable of producing centimeter-scale objects within seconds. A key challenge lies in the calculation of tomographic projection patterns under non-standard conditions, such as the presence of occlusions and materials with diverse optical properties, including varying refractive indices or scattering surfaces.This work demonstrates a broad range of overprinting scenarios, where new structures are directly printed onto or around pre-existing components made from different materials. Our simulations and experimental verifications perform overprinting of absorbing, refracting, reflecting and scattering elements in both round and square vials.All scenarios are optimized with our differentiable, physically based ray-optics approach using the open-source Dr.TVAM framework, delivering high-quality projections for both laser- and LED-based illuminations within minutes and lower-quality projections within seconds, exceeding existing open-source solutions in speed, flexibility, and quality.
    DOI:  https://doi.org/10.1038/s41467-026-73477-3
  13. bioRxiv. 2026 Jun 04. pii: 2026.06.04.729630. [Epub ahead of print]
    Generative design of programmable asymmetric β-barrel nanopores.
    Annika Philomin, Ria Sonigra, Sagardip Majumder, Hsien-Jui Michelin Lin, Yanjing Li, Fanglie Xue, Ryan D Kibler, Brian Coventry, Claire K Baldus, Eva Trapido, Amelie Medeiros, Asim K Bera, Alex Kang, Johnny Mendoza, Manish Kumar, Yi Yang, David Baker.
      Native homo-oligomeric transmembrane β-barrels (TMBs) have been widely explored for molecular sensing, sequencing, and separation applications, but their uniform lumen limits spatial resolution and the localized interactions required for both analyte discrimination and filtration. Monomeric TMBs have been designed using energy-based methods but this has required extensive expert input, limiting scalability and functionality. Here, we present a rapid generative AI method for TMB design that combines diffusion-based backbone generation conditioned on β-barrel structural features with TMB-optimized sequence design. We characterized 48 designs (spanning 10-16 strands) that exhibited measurable conductances pertaining to pore diameters of 0.7-1.5 nm, and determined crystal structures of two designs that have atomic-level agreement with the designed models. We demonstrate the versatility of the generative method by designing nanopores with copper binding sites for selective ion sensing, larger pores that support DNA translocation, and longer pores with increased hydrophobic thickness, that mediate ion transport across three-dimensional networks of monoglyceride bilayers and synthetic polymer-lipid hybrid membranes composed of block copolymers.
    DOI:  https://doi.org/10.64898/2026.06.04.729630
  14. Langmuir. 2026 Jun 09.
    Engineering Dynamic Hydrophobic Domains in Bioreinforced Ionic Hydrogels for Robust and Transparent Soft Electronics.
    Ijaz Ali, Mansoor Khan, Eliaquim B P Sena, André R Fajardo.
      Conductive hydrogels are attractive platforms for soft electronic materials; however, many high-performance systems rely on conductive fillers, complex multinetwork architectures, or multistep processing that compromise scalability and structural clarity. Here, we report a bioreinforced, filler-free ionic hydrogel engineered through micelle-mediated dynamic hydrophobic domains within a hydrogen-bonded polymer network. Stearyl methacrylate is incorporated into a poly(acrylamide) matrix via SDS-assisted micellization, while gelatin serves as a renewable macromolecular reinforcement, establishing a cooperative network governed by reversible hydrophobic associations and extensive hydrogen bonding. This structure-guided design enables efficient energy dissipation and rapid elastic recovery without permanent structural damage. The optimized hydrogel exhibits ultrahigh stretchability (2420%), enhanced fracture stress (0.31 MPa), high optical transparency (∼85.9%), and low mechanical hysteresis, while maintaining stable ionic conductivity through NaCl incorporation. The dynamic network architecture supports reliable electromechanical response over a wide strain range (0.5-650%), with a maximum gauge factor of 12.08, fast response/recovery times, and excellent cyclic durability. Beyond device-level performance, this work demonstrates how controlled micelle-mediated hydrophobic domain engineering in a bioreinforced polymer matrix can generate mechanically robust, transparent, and conductive soft materials without nanofillers or complex processing. The straightforward one-pot synthesis and use of low-cost components highlight the scalability of this platform for next-generation soft electronic and wearable systems.
    DOI:  https://doi.org/10.1021/acs.langmuir.6c01278
  15. ACS Appl Mater Interfaces. 2026 Jun 10.
    Highly Conductive and Durable MXene/CNC/PEDOT:PSS-PNIPAm Hydrogel for Bioinspired Self-Sensing Soft Actuators.
    Luyao Guo, Caixia Sun, Cong Liu, Qingchao Fan, Menghan Xue, Xinhua Xu.
      Living organisms in nature can sensitively perceive environmental stimuli and respond through rapid adaptive deformation. Inspired by this functionality, self-sensing hydrogel actuators have been developed, offering broad potential in areas such as information encryption, flexible wearables, and human-machine interfaces. Here, we report a versatile strategy for fabricating self-sensing hydrogel actuators with simultaneously high electrical conductivity and excellent mechanical durability. A robust interpenetrating network is constructed between surface-functionalized MXene nanomonomers (T-MXene) and modified cellulose nanocrystals (CNC-Vi), which markedly enhances the stability of poly(N-isopropylacrylamide) (PNIPAm) hydrogel. In addition, incorporation of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) further enhances the composite's electrical conductivity while simultaneously improving the environmental adaptability. The resulting hydrogel exhibits high conductivity (14.92 S m-1), remarkable strain sensitivity (GF of 2.17 to 7.23), and outstanding durability. Leveraging these features, we realize reliable information encryption and storage, as well as wearable motion sensors capable of sensitive and precise motion detection. Moreover, the hydrogel system serves as an excellent platform for constructing high-performance self-sensing actuators. By inducing a gradient alignment of T-MXene/CNC-Vi under a direct-current (DC) electric field, we develop a shape-programmable hydrogel actuator that combines rapid responsiveness, remote light-driven actuation, and intrinsic self-sensing capability. This study not only provides a paradigm for designing advanced tactile and self-sensing materials but also establishes a foundation for achieving closed-loop, remotely controlled soft actuators for next-generation intelligent mechanical systems.
    Keywords:  anisotropic structure; flexible wearables; information encryption; programmable shape-morphing; self-sensing actuators
    DOI:  https://doi.org/10.1021/acsami.6c05522
  16. bioRxiv. 2026 Jun 02. pii: 2026.05.29.728696. [Epub ahead of print]
    Physics-guided design of intrinsically disordered proteins.
    Neha Tyagi, Jackson Boodry, Vita Chou, Wilton T Snead, Krishna Shrinivas.
      Intrinsically disordered protein regions (IDPs) are found across the tree of life and characterized by the lack of a stable 3D fold, encoding function through a vast ensemble of conformations. This plasticity makes rational design of IDPs challenging. Physics-based approaches capturing distinct aspects of sequence composition, charge patterning, and molecular interactions have emerged as powerful predictors of ensemble-derived properties. Here, we present a machine learning framework for proteome-scale de novo IDP design by rationally inverting physics-based models. We first program IDPs to tunably sense and respond to diverse biophysical cues and show that IDP ensembles can directly encode complex signal processing, including threshold detection, bandpass filtering, and Boolean-type multi-input logic. We next engineer multicomponent IDP mixtures with tailored emergent condensate properties, including layering and number of phases, compositional specificity, and RNA-dependent remodeling of structure and composition. Finally, we demonstrate designed IDPs that selectively partition into or deplete from biological condensates in living cells. Together, our framework establishes a flexible and scalable strategy for design of ensemble-derived and collective properties in dynamic biomolecules.
    DOI:  https://doi.org/10.64898/2026.05.29.728696
  17. Proc Natl Acad Sci U S A. 2026 Jun 16. 123(24): e2533437123
    A biomineralized light-guiding structure in the porous calcitic skeleton of the sea star Protoreaster nodosus.
    Liuni Chen, Hannah Feldstein, Zian Jia, Chenhao Hu, Hongshun Chen, Yang Geng, Emily M Peterman, Carla Slebodnick, Daniel I Speiser, Daniel Baum, Mathias Kolle, Ling Li.
      Biomineralized structures produced by living organisms are widely recognized for their exceptional mechanical performance, yet their potential optical roles are relatively less explored. Here, we demonstrate that within the calcitic ossicle-based skeleton of the sea star Protoreaster nodosus, where each ossicle represents a discrete skeletal element, one specialized ossicle, known as the terminal plate, contains a radially arranged array of light-guiding structures (LGSs). These LGSs exhibit an elongated, cone-like geometry (~250 μm in length) and are embedded within the porous stereom, a characteristic meshwork architecture of echinoderms analogous to open-cell cellular solids and composed of magnesium-containing single-crystalline calcite. Optical experiments demonstrate that, unlike other skeletal elements, the terminal plate can transmit and focus light into an internal cavity via the LGS array. Combined optical analyses using ray-tracing and finite-difference time-domain simulations reveal that each LGS transmits ca. 70% of incident light at normal incidence and concentrates it up to 2.8-fold at its exiting surface. Furthermore, when acting collectively as the LGS array within the terminal plate, the LGSs capture light over a broad field of view (~120°), resulting in an integrated transmitted intensity that is sixfold to eightfold greater than the incoming intensity perceived by a single LGS. Although the biological function of this optical capability remains uncertain, this natural porous structure demonstrates that cellular solids can integrate efficient light-guiding behavior while enhancing mechanical properties (i.e., threefold increase in stiffness compared with random stereom), offering design insights for lightweight, multifunctional structures.
    Keywords:  bio-optical structures; biomineral; echinoderm; microstructure; multifunctionality
    DOI:  https://doi.org/10.1073/pnas.2533437123
  18. J R Soc Interface. 2026 Jun 10. pii: 20251094. [Epub ahead of print]23(239):
    Artificial morphogenesis of curved surface structures inspired by differential growth in biology.
    Kentaro Morikawa, Takumi Nakamura, Yoshihiko Matsumoto, Keisuke Matsuda, Masakazu Akiyama, Shintaro Yamasaki, Shigeru Kondo, Yasuhiro Inoue.
      From the elegant petals of flowers to advanced aerospace designs, curved surfaces are fundamental to both natural and engineered systems, playing critical roles in structural and functional performance. In biology, these surfaces frequently arise from differential growth processes, where spatially varying growth rates orchestrate the transformation of flat tissues into intricate three-dimensional forms, exemplified by leaf curling or organ development. Engineering such surfaces, however, remains challenging, as current methods are energy-intensive, material-heavy, and lack the efficiency and adaptability seen in natural systems. Here, we demonstrate an artificial morphogenesis methodology that fabricates curved surfaces from planar materials by programming area change rates calculated through conformal mapping. Using heat-shrink film, we three-dimensionally-printed precisely patterned non-shrinking elements to implement calculated area change rate distributions, ensuring precision and reproducibility. This method enables the design and production of diverse target shapes using adaptable materials that maintain their shape even in dry environments. Compared with conventional techniques, this approach reduces material waste, eliminates the need for moulds and offers high adaptability. This bioinspired framework bridges biological principles with modern fabrication techniques, advancing curved surface design. Potential applications include adaptive medical implants for minimally invasive surgeries, lightweight aerospace structures and soft robotic skins with real-time adaptability.
    Keywords:  4D printing; biomimetics; computational fabrication; computational geometry; conformal map; morphogenesis
    DOI:  https://doi.org/10.1098/rsif.2025.1094
  19. Adv Mater. 2026 Jun 10. e73669
    Soft Hardware, Flowing Software: Reconfigurable Microfluidics for Adaptable Chemical Computation.
    Piet J M Swinkels, Brigitta Dúzs, Oliver Skarsetz, Kohei Nishiyama, Andreas Walther.
      Chemical and physical computing systems promise information processing in performance regimes inaccessible to conventional electronics. However, they are typically constrained by static hardware architectures that limit adaptability and computational richness. Here, we introduce a reconfigurable microfluidic platform where soft hydrogel structures are 3D-printed and erased in situ to dynamically reshape the physical environment in which chemical computation occurs. By treating microfluidic geometry as an active, programmable element rather than a passive container, we demonstrate hardware-reconfigurable control over chemical information processing. We demonstrate switchable Deoxyribonucleic acid (DNA) logic gates that alternate between AND and OR functionality without modifying the underlying reaction network, decoupling logic function from molecular composition. Extending this to a non-equilibrium chemical reaction network in the form of a feedback-controlled pH oscillator, we demonstrate that printed structures steer reaction kinetics and spatial pattern formation, giving rise to geometry-dependent spatiotemporal states. Leveraging these dynamics, we implement a physical reservoir computer in which reconfigurable microfluidic hardware enables the realization of diverse nonlinear functions through simple linear readout. Our work establishes reconfigurable soft microfluidic hardware as a control layer for chemical computation, highlighting how adaptable physical environments actively expand the computational state space of chemical software.
    Keywords:  3D printing; DNA nanotechnology; chemical reaction network theory; computation; computer science; logic gate; microfluidics; reservoir computing; smart hydrogels; software
    DOI:  https://doi.org/10.1002/adma.73669
  20. bioRxiv. 2026 Jun 02. pii: 2026.06.01.729353. [Epub ahead of print]
    MARBL: A Live-Cell Method for Profiling Bioenergetic Heterogeneity by Noncanonical Methionine Labeling of the Cell Surface Proteome.
    Lillian R Delacruz, Ming Ye, Kendra A Libby, Keran Han, Chad J Munger, Yunping Qiu, Irwin J Kurland, Alison E Ringel.
      Heterogeneity is a hallmark of biological systems, where cell-to-cell variability supports adaptation to changing environments, but also enables maladaptive states such as drug resistance. Many sources of non-genetic variation, particularly bioenergetics and metabolism, remain difficult to measure in living cells and connect to functional outcomes. Here, we introduce MARBL (Methionine Analogues for Ratiometric Bioenergetics in Live cells), a method that encodes translationally-coupled energetic responses to metabolic stress as an internally normalized signal within the surface proteome of living cells. Applying MARBL to primary immune cells reveals that differences in baseline translational activity can underlie apparent metabolic vulnerabilities, underscoring the importance of ratiometric measurements. We demonstrate that MARBL can enrich pathogenic from non-pathogenic TH17 cells based on resilience to bioenergetic stress, which functionally distinguishes cells that produce IFNγ upon restimulation. Overall, MARBL offers a versatile platform to profile metabolic resilience in living cells and link bioenergetic state to cellular function.
    DOI:  https://doi.org/10.64898/2026.06.01.729353
  21. PRX Life. 2025 Sep;pii: 033011. [Epub ahead of print]3(3):
    Sticky enzymes: increased metabolic efficiency via substrate-dependent enzyme clustering.
    Alejandro Martínez-Calvo, Jello Zhou, Yaojun Zhang, Ned S Wingreen.
      Coclustering of subsequent enzymes in a pathway can accelerate the processing of metabolic intermediates, with benefits including increased pathway fluxes, reduced toxicity, and sensitive branch-point regulation. While the optimal organization of such clusters has been explored theoretically, little is known about how to achieve such organization inside cells. Here we propose that phase-separating enzymes can self-organize into nearly-optimally sized and spaced clusters, provided that their "stickiness" is regulated by local substrate availability. In a nutshell, enzyme clusters only form when and where they are needed to process substrate. We study a mathematical model that implements this scheme for simple metabolic pathways, including all thermodynamic constraints. We find that pathway fluxes can be increased by 50 to 1000-fold and toxic metabolites can be decreased by 10 to 100-fold, at realistic enzyme densities. Finally, we discuss how enzyme "stickiness" could be allosterically regulated. This study presents a self-organization strategy that goes beyond current paradigms for natural and engineered enzyme clusters, and thus represents a motivating challenge to the fields of synthetic biology and metabolic engineering.
    DOI:  https://doi.org/10.1103/99bt-4ss4
  22. iScience. 2026 Jun 19. 29(6): 116191
    Comprehensive mechanical reinforcement of hydrogels via network refinement.
    Han Li, Zidi Zhou, Yuan Gao, Jincheng Lei, Zishun Liu.
      Traditional single-network hydrogels are limited by trade-offs among key mechanical properties, such as elastic modulus and toughness, and are further compromised by structural defects introduced during synthesis. These constraints significantly hinder their performance in demanding applications. Here, we propose a network-refinement strategy using repeated crosslinking to achieve comprehensive mechanical reinforcement. Through network refinement, structural defects within polymer networks are progressively filled, and both the network homogeneity and effective chain density are improved. The reinforced hydrogels exhibit up to a 6-fold increase in elastic modulus, a 10-fold enhancement in fracture toughness, a 20-fold increase in tensile strength, and a 42-fold improvement in work of fracture, while maintaining high stretchability and negligible hysteresis under moderate deformation. This universal strategy provides an effective route to comprehensively enhance the mechanical properties of hydrogel-like materials, paving the way for robust soft materials in applications such as cardiac healing patches, load-bearing biomedical implants, and wearable electronics.
    Keywords:  Materials science; Mechanical property; Polymers
    DOI:  https://doi.org/10.1016/j.isci.2026.116191
  23. Molecules. 2026 Jun 04. pii: 1958. [Epub ahead of print]31(11):
    High-Resolution 3D Bioprinted Hydrogel Scaffolds Enable Sustained Intraperitoneal Cell Delivery.
    Yu Zhang, Lauren E Carlberg, Cali N Colliver, Alain Valdivia, Morrent Thang, Caroline A Stockwell, Jillian L Perry, Shawn D Hingtgen.
      Intraperitoneal (I.P.) delivery of cell-based therapeutics represents a promising strategy for treating regional peritoneal diseases; however, rapid cellular clearance severely limits therapeutic durability. A critical unmet need is the development of implantable biomaterial platforms that can both mechanically integrate within the dynamic I.P. cavity and sustain viable cell persistence in vivo. Here, we establish a Continuous Liquid Interface Production (CLIP)-based 3D bioprinting strategy to engineer transplantable, cell-laden hydrogel scaffolds optimized for I.P. implantation. Through systematic bioresin design, we identify a GelMA-PEGDA formulation that achieves a balance between high-resolution printability, tissue-matched mechanical characteristics (Young's modulus 10-15 kPa), and controlled biodegradation (~75% mass loss over 14 days). The resulting constructs support sustained cell viability and proliferation for over 30 days in vitro. Importantly, in an animal study conducted in 6-8 weeks of female nude mice, in vivo I.P. implantation demonstrates a ~10-fold extension in cellular persistence compared to direct cell injection, prolonging the time to 50% signal decay from ~3 days to ~30 days, with detectable cell retention approaching two months in select animals. The platform further accommodates multiple clinically relevant cell types, including human mesenchymal stem cells and neural stem cells, highlighting its translational versatility. Collectively, this work defines key material and architectural parameters required for I.P. implantable cell therapeutics and establishes CLIP-based bioprinting as a scalable strategy for regional delivery of living therapeutics.
    Keywords:  3D bioprinting; Continuous Liquid Interface Printing (CLIP); cell delivery; hydrogel scaffolds; intraperitoneal implant
    DOI:  https://doi.org/10.3390/molecules31111958
  24. ACS Appl Mater Interfaces. 2026 Jun 12.
    Cellulosic Hydrogels Comprising Cellulose Nanocrystals or Chitin Nanocrystals for Historic Ceramic Conservation.
    Madalen Azpitarte Aretxabaleta, Marta García-Castrillo, Laura García Boullosa, Sonia Aníbarro Sánchez, Dorleta Jimenez de Aberasturi, Erlantz Lizundia.
      Over time, antique ceramics undergo a series of chemical and physical degradation processes, such as salt crystallization or the accumulation of atmospheric pollutants, which compromise their structural and aesthetic integrity. To restore and conserve cultural heritage artifacts, polymeric gels have been developed, where, in comparison to conventional petroleum-derived materials, naturally occurring polymers offer enhanced properties in terms of tunable viscoelasticity, high water retention capacities, low toxicity, and inherent biodegradability. Accordingly, here, we develop nanocomposite gels based on hydroxypropyl cellulose and incorporated biocolloids with anionic and cationic surface charges, cellulose nanocrystals (CNCs), or chitin nanocrystals (ChNCs). To enhance the durability and ductility of the hydrogels, chemical cross-linking with citric acid and plasticization with ethylene glycol are performed. Tunable Young's modulus (17.2-145.4 MPa) and elongation at break (14.3-109.1%) are obtained. Cleaning studies are carried out on actual 17th-19th century ancient ceramics from an archeological site in Bizkaia (Basque Country, Northern Spain). The hydrogels are applied directly onto the ceramics to set a continuous solid-liquid interface with no need for external mechanical pressure. X-ray fluorescence results reveal the hydrogels removing up to 72% of the lead in ceramics in 8 h of treatment, making those materials particularly suitable to remove traces of hazardous substances that are integral materials in various traditional crafts and cultural heritage artifacts. The strategy of incorporating biobased colloids within a cellulosic hydrogel allows for tuning its chemical and physical properties and introduces additional hydroxyl and amine/acetamide moieties that act as Lewis bases to enable chelation and electrostatic attraction effects for the cleaning process.
    Keywords:  ancient ceramics; cultural conservation; cultural heritage; nanocellulose; nanochitin; renewable materials
    DOI:  https://doi.org/10.1021/acsami.6c05573
  25. ACS Appl Mater Interfaces. 2026 Jun 10.
    Loach-Inspired Lubricant and Antibacterial Hydrogels with Thermochromism for Multifunctional Coatings.
    Hai Wang, Yang Gao, Junnan Zhao, Shangheng Li, Xingyu Liu, Yuanrui Wang, Guanghui Gao.
      Hydrogels with brilliant hydrophilicity and prominent biocompatibility are among the promising coating materials with engineering applications; however, they are still facing significant challenges in terms of multifunctional integration. Herein, inspired by loach, a multifunctional hydrogel with comprehensive advantages of lubricity, bacteriostasis, thermochromism, and antifouling property is successfully constructed by introducing loach mucus. The polyacrylamide/sodium hyaluronate (PAAm/HA) network was selected as the primary framework to provide fundamental mechanical properties. By replacing the water solvent with the extracted loach mucus, we can improve the mechanical property and achieve high lubricity and bacteriostasis of the hydrogel. The hydrogel exhibits a low friction coefficient in various solvent environments and has inhibitory effects on both Gram-negative and Gram-positive bacteria. Meanwhile, the hydrogel was proven to be antifouling. Furthermore, the inclusion of dopamine not only forms stable amide bonds with the carboxyl groups on HA but also serves as an adhesive moiety to allow the hydrogel to attach to diverse substrates, thus improving the hydrophilicity and lubrication of the target substrate. Besides, the crystallization properties of gluconate at low temperatures enable the hydrogel to undergo a thermochromic transparent-opaque transition. This work opens up an avenue for the rational design of multifunctional hydrogel coatings, which can be used for drag reduction in medical devices and privacy protection in smart windows.
    Keywords:  antibacterial; hydrogel coating; loach-inspired; lubricant; thermochromic
    DOI:  https://doi.org/10.1021/acsami.6c05244
  26. bioRxiv. 2026 Jun 02. pii: 2026.05.29.728820. [Epub ahead of print]
    Alginate-Coated Collagen Hydrogel Tubes for Scalable Cell and Biotherapeutic Particle Manufacturing.
    Xinran Wu, Ying Pan, Yakun Yang, Li Han, Yong Wang, Aziza P Manceur, Yuguo Lei.
      Efficient, scalable, and cost-effective production of mammalian cells and biotherapeutic particles remains a major challenge for both research and clinical applications. Conventional 2D and 3D culture systems suffer from low volumetric yields, poor scalability, and high costs. Previously, we developed collagen hydrogel tube microbioreactors (ColTubes) that support high-density, high-viability cell culture by preventing excessive cell aggregation and minimizing hydrodynamic stress. However, ColTubes exhibit adhesion to culture vessels and to each other, and leaked cells frequently attach to outer tube surfaces - behaviors that would limit scalability. Here we introduce AlgColTubes: collagen hydrogel tubes coated with a thin, ionically crosslinked alginate layer to overcome these limitations. Scanning electron microscopy confirms that alginate penetrates the collagen wall and forms a stable interpenetrating hydrogel network, whose depth can be tuned by coating concentration and duration. The alginate coating remains structurally intact under static and dynamic culture conditions without impairing nutrient transport or cell growth. AlgColTubes eliminate tube-tube and tube-vessel adhesion, and prevent exogenous cell attachment to the outer surface, while maintaining cell viability and proliferation comparable to uncoated ColTubes. Their unique architecture - an adhesive collagen interior and non-adhesive alginate exterior - further enables a truncated-tube format for continuous release of biotherapeutic particles through open tube ends. We demonstrate that lentivirus is released from truncated AlgColTubes in a segment length-dependent manner, reaching ~100% release efficiency at 1-mm segment lengths. AlgColTubes provide a scalable, cost-effective platform for high-yield cell and particle manufacturing, with broad potential across basic research, translational studies, and industrial bioprocessing.
    DOI:  https://doi.org/10.64898/2026.05.29.728820
  27. bioRxiv. 2026 Jun 06. pii: 2026.06.02.729677. [Epub ahead of print]
    Nonlinear rheology of laminin-111-modified hyaluronan hydrogels.
    Jordan L Shivers, Mary C Farach-Carson, Fred C MacKintosh, Danielle Wu.
      We experimentally assess the nonlinear rheology of composite biopolymer hydrogels composed of thiolated hyaluronic acid, poly(ethylene glycol) diacrylate (PEGDA), and laminin-111 in varied concentrations. We focus in particular on the influence of laminin on the mechanics of the assembled hydrogels, reporting nonlinear rheological measurements for gels under applied shear and compressive load. We find that increasing the concentration of laminin in the synthesized gels reduces the linear shear modulus and gives rise to a mild strain softening regime at intermediate strains prior to the onset of strain stiffening. In the stiffening regime, we find that all gels exhibit stress-controlled mechanics with K ∝ σ a , with an apparent stiffening exponent of a ≈ 1, in agreement with observations of a variety of other reconstituted biopolymer gels. We discuss the possible implications of this nonlinear mechanical behavior on mechanotransduction and organoid development in biomimetic extracellular matrices.
    DOI:  https://doi.org/10.64898/2026.06.02.729677
  28. STAR Protoc. 2026 Jun 09. pii: S2666-1667(26)00259-5. [Epub ahead of print]7(2): 104606
    Protocol for synthesis and mechanical characterization of polyacrylamide hydrogels of varying stiffness for cell culture applications.
    Charlotte Cresens, Samet Aytekin, Behrad Shaghaghi, Lotte Gerrits, Ana Montero-Calle, Rodrigo Barderas, Paul Kouwer, Susana Rocha.
      The impact of mechanical cues on cell behavior is increasingly being recognized, rendering hydrogel platforms that mimic the extracellular matrix indispensable in in vitro cell biology research. Here, we present a protocol for the synthesis and rheological characterization of polyacrylamide (PAAm) hydrogels with varying stiffnesses, produced as large, circular, unattached gels customizable in shape and size. We outline techniques for their use in cell culture and downstream applications involving secretome or cell analysis and protein visualization by fluorescence microscopy. For complete details on the use and execution of this protocol, please refer to Cresens et al.1.
    Keywords:  Biotechnology and bioengineering; Cell culture; Cell-based Assays; High Throughput Screening; Material sciences; Molecular Biology; Protein expression and purification
    DOI:  https://doi.org/10.1016/j.xpro.2026.104606
  29. Nat Commun. 2026 Jun 10.
    Synthetically designed anti-defense proteins overcome barriers to bacterial transformation and phage infection.
    Jeremy Garb, David W Adams, Eliane Hadas Yardeni, Melanie Blokesch, Rotem Sorek.
      Bacterial defense systems present considerable barriers to both phage infection and plasmid transformation. These systems target mobile genetic elements, limiting the efficacy of bacteriophage-based therapies and restricting genetic engineering applications. Here, we employ a de-novo protein design approach to generate proteins that bind and inhibit bacterial defense systems. We show that our synthetically designed proteins block defense, and that phages engineered to encode the synthetic proteins can replicate in cells that express the respective defense system. We further demonstrate that a single phage could be engineered with multiple anti-defense proteins, yielding improved infectivity in bacterial strains carrying multiple defense systems. Finally, we show that plasmids that express synthetic anti-defense proteins can be introduced into bacteria that naturally restrict plasmid transformation. Our approach can broaden host ranges of therapeutic phages and can improve genetic engineering efficiency in strains that are typically difficult to transform.
    DOI:  https://doi.org/10.1038/s41467-026-74301-8
  30. Polym Sci Technol. 2026 Jan 27. 2(1): 6-21
    Bio-Inspired and Protein-Based Elastomeric Materials.
    Xiaodong Han, Juanjuan Su, Jingjing Li, Hongjie Zhang, Kai Liu.
      Natural structural-protein-based elastomeric materials have garnered significant attention as potential alternatives to synthetic polymers, due to their remarkable biodegradability, biocompatibility, and low immunogenicity as well as their exceptional mechanical performance with high resilience, energy storage capacity, and fatigue resistance. However, the biosynthesis of artificially engineered elastomeric proteins and fabrication of elastomeric materials with on-demand properties remain great challenges, particularly in the context of designing and governing the hierarchical structure of protein assemblies. To understand the essence of mechanical properties and maximize the potential of protein-based elastomeric materials, this review systematically explores the sources and molecular mechanisms for elastic performance of a diverse range of natural elastomeric proteins. Subsequently, we discuss the design, biosynthesis, and rational assembly strategies of artificially engineered elastomeric proteins with specific secondary structures. Finally, we address the current challenges and provide perspectives on the development of next-generation protein-based elastomeric materials.
    Keywords:  Artificially engineered protein; Biomedical application; Elastomeric material; Mechanical property; Structural protein
    DOI:  https://doi.org/10.1021/polymscitech.5c00054
  31. Sci Adv. 2026 Jun 12. 12(24): eaeb1989
    Hierarchical laser-programmed soft actuators for designing bionic robots with freeform morphing shapes.
    Yuhan Guo, Mingguang Han, Weixiong Yang, Meihong He, Haibin Duan, Xilun Ding, Sida Luo.
      Bio-inspired shape-morphing structures, essential for next-generation soft robotics with unprecedented adaptability, demand actuators capable of complex and configurable three-dimensional motions. By overcoming traditional stimulus-responsive strategies facing the trade-off between manufacturing simplicity and kinematic sophistication, here, we introduce a spatially differentiated laser-programming technology for digital manufacturing laser-induced graphene-based soft actuators (LIG-SAs) with freeform morphing capabilities. Via cross-scale control of lasing energy and scribing direction, material heterogeneity and structural hierarchy can be tuned simultaneously for introducing decoupled electrothermal distribution and stiffness anisotropy, thus encoding LIG-SAs with four typical motion units: straight bending, directional curling, rigid supporting, and soft connecting. By arbitrarily grouping multimodal morphing units into concretized devices, this approach further empowers freeform design of bionic robots including octopus-like tentacles and inchworm/seal-like crawlers toward multitask locomotion of conformal grasping, path navigation, and obstacle avoidance. This framework bridges digital design with physical intelligence, unlocking previously unidentified avenues of soft robots for creating sophisticated and programmable morphologies.
    DOI:  https://doi.org/10.1126/sciadv.aeb1989
  32. Nat Commun. 2026 Jun 08.
    Multi-scale structural engineering enables ultra-strong and tough eutectogels.
    Ning Tang, Yanlong Yin, Hao Zhang, Jianhua Tang, Ousheng Zhang, Jigang Yang, Jun Hu.
      Achieving simultaneous enhancement of strength, stiffness, and toughness in polymer gels remains a fundamental challenge due to the thermodynamic incompatibility between energy storage and energy dissipation. Here, we present a multi-scale regulation approach that synergistically integrates directional annealing with deep eutectic solvent-mediated solvent exchange to precisely modulate the polymer network at molecular, nanoscale, and microscale levels. This coordinated hierarchical design yielded poly(vinyl alcohol) eutectogels exhibiting exceptional tensile strength of 62.2 ± 1.8 MPa, a Young's modulus of 355.3 ± 32.9 MPa, and a toughness of 179.0 ± 11.1 MJ m-3, representing 311-, 11843-, and 597-fold enhancements over the original hydrogel, respectively. The synergistic effects of enhanced interchain hydrogen bonding, crystalline domain formation, and anisotropic network alignment enabled high fracture resistance (131.5 ± 2.3 kJ m-2), fatigue threshold of 15.9 kJ m-2, and damping efficiency of 95.8%, providing robust protection against impact-induced damage. The multi-scale regulation strategy not only offers a promising solution to overcome the conventional trade-offs in mechanical properties, but also establishes universal principles for the design of next-generation soft materials, with significant potential for applications in flexible electronics, wearable devices, and advanced impact-resistant systems.
    DOI:  https://doi.org/10.1038/s41467-026-74246-y
  33. Nat Commun. 2026 Jun 11.
    Layer-by-layer shear densification for multiscale hierarchical alignment in bulk hydrogels.
    Sen Wang, Senxuan Tang, Tianqi Fu, Yirong Jiang, Yun Lin, Lianlian Fu, Ronghui Wu, Youhui Lin.
      Natural structural tissues achieve exceptional performance through precisely aligned hierarchical architectures that extend across multiple length scales. However, realizing such multiscale long-range alignment in synthetic bulk hydrogels remains challenging because of the difficulty in constructing a uniformly dense and highly oriented structure that extends throughout the full bulk matrix. Here, we introduce a scalable and versatile Layer-by-Layer Shear Densification (LBSD) strategy that integrates flocculation-induced aggregation with shear-driven progressive alignment, precisely driving the architectural evolution toward compact and uniformly ordered lamellar structures across multiscales. The resulting poly(vinyl alcohol) (PVA) hydrogels with a hierarchical network exhibit a Herman's orientation factor of 0.91, surpassing previously reported values for bulk hydrogels. The structural orientation enables the hydrogel to exhibit excellent mechanical properties, including a tensile strength of 41.29 ± 2.10 MPa and toughness of 159.37 ± 28.15 MJ·m⁻³. To demonstrate the versatility, this strategy is further used to fabricate gelatin hydrogels, resulting in a 32-fold enhancement in toughness. Anisotropic thermal conductivity, another representative physical property originating from molecular-level alignment, is also demonstrated. This work establishes a generalizable technology for developing high-performance bulk polymeric materials through molecular-level engineering, offering substantial potential for applications in load-bearing components, bioelectronic devices, thermal management systems, etc.
    DOI:  https://doi.org/10.1038/s41467-026-74146-1
  34. Biosens Bioelectron. 2026 Jun 04. pii: S0956-5663(26)00519-1. [Epub ahead of print]311 118887
    Target-triggered assembly of engineered bacteria enables dual-mode detection of microRNA.
    Xuemei Wang, Ye Li, Heng Zhou, Yating Sun, Lie Li, Jianwei Jiao, Xiangjiao Meng, Jin Jiao.
      Engineered bacteria offer unique opportunities for biosensing because they combine genetically programmable biological activity with tunable surface interfaces. However, constructing living sensing systems that enable programmable recognition, reliable signal output, and robust performance in complex samples remains challenging. Here, we report an interfacially engineered bacterial sensing platform for dual-mode microRNA detection. Engineered Escherichia coli expressing enhanced green fluorescent protein (eGFP) were used as living signal carriers, and a polyphenol coating was deposited to create a stable, functionalizable interface. This coating preserved bacterial fluorescence while enabling immobilization of nucleic acid hairpin probes. Upon target recognition, catalytic hairpin assembly (CHA) was triggered, driving the programmable bridging and aggregation between bacteria and magnetic beads. This process converts molecular recognition into a magnetically separable assembly event, enabling target enrichment and background reduction. Meanwhile, enriched bacteria provide fluorescence output via intracellular eGFP, while Fe3+ released from the coating under acidic conditions generates a Prussian blue colorimetric signal. Together, these processes establish a fluorescence-colorimetric dual-mode sensing platform with limits of detection of 5.33 pM for the fluorescence mode and 14.1 pM for the colorimetric mode. In serum samples from glioma patients, the platform effectively distinguished patients from healthy controls, with dual-mode analysis showing improved discrimination performance compared to single-mode detection. This work demonstrates that interfacial engineering transforms engineered bacteria into multifunctional living sensing units and provides a practical strategy for developing reliable biosensing systems for liquid biopsy applications.
    Keywords:  Catalytic hairpin assembly; Dual-mode biosensing; Engineered bacteria; Interfacial engineering; microRNA detection
    DOI:  https://doi.org/10.1016/j.bios.2026.118887
  35. Biofabrication. 2026 Jun 11.
    Generic optimization procedure for high-resolution printing by stereolithography of 3D scaffolds compatible for cell culture applied to a small intestinal architecture.
    Elise Ponthier, Lucien Guth, Sandra Pérez-Domínguez, Julie Foncy, Daniel Ferri-Angulo, Arnaud Besson, Laurent Malaquin.
      Stereolithography is now widely used in tissue engineering since it allows fine-tuning of geometry and mechanical properties to mimic the topography of tissues. However, most published studies do not detail the optimization protocols that have been used to obtain these structures. Here, we developed a generic process to print photosensitive biomaterial formulations by stereolithography to obtain a specific topography. Using the small intestine architecture as a model combining filled villi and hollow crypts, we identify key parameters that govern both printing resolution and cellular behavior. Moreover, we highlight the impact of absence of oxygen inhibition and light penetration depth in cavities, causing partially crosslinked material within crypts. This issue was resolved by adding tartrazine, a biocompatible photoabsorber that restricts crosslinking depth. Our stereolithography (SLA) process allows the fabrication of intestinal models with a high precision level and the reproduction of crypt and villi structures with physiologic dimensions and high structural integrity. We show that Caco-2 cells adhere, colonize, polarize and differentiate on the printed scaffolds over 20 days of culture. The developed models could subsequently be adapted to support intestinal organoid growth and be integrated in microfluidic chips to implement mechanical and biochemical cues, representing a more physiological model with accurate dimensions to study intestinal diseases.Overall, this study provides a transferable framework for optimizing stereolithographic printing of hydrogel-based topographies allowing precise control of substrate properties for tissue engineering.
    Keywords:  3D Printing; Hydrogel; PEGDA/GelMA; Small intestine; Stereolithography
    DOI:  https://doi.org/10.1088/1758-5090/ae7c36
  36. Proc Natl Acad Sci U S A. 2026 Jun 16. 123(24): e2602147123
    Programmable DNA hydrogels for dual-mode PD-L1 suppression via polyvalent LYTAC mimics and transcriptional silencing.
    Rui Zhang, Jing Wang, Shuo Wu, Xinghong Shen, Feng Xiao, Xingyu Jiang, Chi Yao, Dayong Yang.
      Immune checkpoint blockade has revolutionized oncology, yet low response rates and acquired resistance-often driven by inadequate Programmed death-ligand 1 (PD-L1) suppression-remain significant barriers. While degradation-based proteolysis-targeting chimeras offer a promising alternative to traditional antibodies, targeting the intracellular and transcriptional drivers of checkpoint expression remains a challenge. We report a programmable, tumor-responsive DNA hydrogel platform, synthesized via rolling circle amplification, designed for the comprehensive, dual-mode modulation of PD-L1. This modular nucleic acid framework codelivers polyvalent aptamer-based lysosome-targeting chimeras (LYTAC mimics) to induce extracellular PD-L1 degradation and siSMARCAL1 to silence the chromatin-remodeling-driven transcriptional activation of PD-L1. By integrating localized, sequential release within the tumor microenvironment, this system achieves a synergistic "degrade-and-silence" effect that effectively dismantles PD-1/PD-L1-mediated immunosuppression while concurrently triggering immunogenic cell death. In murine melanoma models, the hydrogel significantly suppressed primary tumor growth and prevented postoperative recurrence, eliciting a robust and durable systemic antitumor immune response. Our findings establish a versatile, DNA-based materials strategy for programmable protein degradation and multilevel checkpoint modulation, offering a generalizable approach for enhancing the efficacy of cancer immunotherapy.
    Keywords:  DNA hydrogel; DNA nanotechnology; PD-L1; cancer immunotherapy; lysosome-targeting chimeras (LYTACs)
    DOI:  https://doi.org/10.1073/pnas.2602147123
  37. ACS Biomater Sci Eng. 2026 Jun 09.
    A Methodological Approach to Relate Pentapeptide Sequence, Atomistic Self-Assembly, and Gelation Behavior.
    Shimanto Roy, Robin K Hur, Lawrence C McAllister, Kyle J Lampe, Camille L Bilodeau.
      The development of biomaterials that mimic the extracellular matrix of the native tissue represents an exciting frontier for tissue engineering and regenerative medicine. Injectable hydrogels made of short, self-assembling peptides offer a promising platform for the delivery and directed differentiation of therapeutic stem cells. However, the rational design of peptide hydrogels remains a significant challenge in tissue engineering due to our lack of understanding of the molecular mechanisms that underlie self-assembly. Although these materials hold great promise, most computational design efforts have focused on studying how peptide sequence impacts aggregation propensity. While useful as an initial indicator of self-assembly, aggregation propensity can be misleading as it is nearly synonymous with hydrophobic precipitation, thus highlighting the need for more robust screening and design strategies. To address this limitation, we introduce a systematic approach to study self-assembly beyond aggregation via molecular dynamics for designing peptide hydrogels. Our approach introduces several new atomistic descriptors-end-to-end distance, π-π stacking interactions, and residue-specific contacts-derived from molecular dynamics simulations to capture the nuances of the sequence-dependent assembly. We additionally uncovered key interactions among hydrophobic, aromatic, and charged residues that reliably predict gel formation, enabling a more rational approach to hydrogel design. We apply these molecular features to successfully predict a previously undiscovered, yet robust self-assembling sequence, KYYYL. An analysis of variance (ANOVA) confirms that our parameters provide significant differences among sequences, whereas aggregation propensity failed to reject the null hypothesis. Finally, we establish the sensitivity of simulation parameters to ensure methodological rigor and enable future study expansion in peptide sequence space. Our findings reveal that amino acid selection and position influence self-assembly. Furthermore, we demonstrate the key interactions among varying residues that reliably predict gel formation, enabling a more rational approach to supramolecular hydrogel design.
    Keywords:  biomaterials; dynamics; hydrogel; modeling; peptide
    DOI:  https://doi.org/10.1021/acsbiomaterials.6c00402
  38. ACS Nano. 2026 Jun 10.
    Nanodroplet-Confined Electroplating Enables Submicron Printing of Metals and Oxide Ceramics.
    Mirco Nydegger, Rebecca A Gallivan, Arthur Barras, Henning Galinski, Ralph Spolenak.
      The fabrication of functional micro- and nanoelectronic devices requires the deposition of high-quality materials from different electronic material classes, such as conductors, semiconductors, and insulators. Establishing ultrahigh-resolution additive manufacturing as a viable addition to existing fabrication methods requires the combinatorial additive deposition of different electronic material classes. However, current techniques do not provide such a capability. Here, we demonstrate that droplet-confined electroplating, an ultrahigh-resolution additive manufacturing technique initially developed for metals as electrohydrodynamic redox printing (EHD-RP), allows the direct deposition of not only many metals but also metal oxides. Particularly, we demonstrate that applying fundamental electrochemical principles in combination with on-the-fly switching of the deposited material allows for the direct codeposition of metals, metal hydroxides, and metal oxides. Our results demonstrate the feasibility of leveraging simple water-based electrochemical concepts to produce intricate and multimaterial structures at the nanoscale.
    Keywords:  3D nanofabrication; EHD-RP; electrohydrodynamic ejection; metal nanostructures; microscale additive manufacturing
    DOI:  https://doi.org/10.1021/acsnano.6c01486
  39. Nat Nanotechnol. 2026 Jun 11.
    Advancing mechanobiology from single molecules to complex cellular systems.
    Krishna Chaitanya Kasuba, Gotthold Fläschner, Akanksha Jain, Michael Krieg, Upnishad Sharma, Valentin Gensbittel, Michele M Nava, Miguel Camacho Rufino, Barbara Treutlein, Prisca Liberali, Xavier Trepat, Frank Jülicher, Matthieu Piel, Dagmar Iber, Matthias P Lutolf, Botond Roska, Massimo Vassalli, Daniel J Müller.
      Cells operate as networks of proteins, membranes, condensates and compartments, each sensing and displaying distinct intracellular mechanical properties. However, cells also sense, adapt and respond to manifold mechanical properties of the environment, including adhesion, tension, stiffness, shear, viscoelasticity, plasticity, pressure and confinement. By gauging these properties at various timescales and across nano to macro length scales, cellular systems alter their collective responses. The field of mechanobiology aims to elucidate how cellular systems such as tissues, organoids or organs perceive, respond to and influence mechanical cues, and how these impact physiological processes including homeostasis, growth, division, differentiation, movement, development, adaptation and apoptosis. This Perspective highlights challenges within mechanobiology that must be systematically tackled to advance exploration and deepen our understanding of the mechanical attributes of intricate multicellular organisms. Such understanding necessitates the engineering of multicellular models as reference systems, the development of new tools to rigorously quantify and manipulate mechanical properties from the nanoscale to macroscale and theoretical frameworks to decode mechanobiological complexities. Ultimately, addressing these challenges will improve the analysis, monitoring and prediction of mechanobiological processes across molecular, multicellular and organismal scales, thus advancing mechanodiagnostics and mechanomedicine.
    DOI:  https://doi.org/10.1038/s41565-026-02179-0
  40. Polym Sci Technol. 2025 Nov 25. 1(9): 748-771
    Bioinspired Real-Time Dynamic Responsive Structural Colors.
    Zekun Zhang, Xiaoyu Hou, Mingzhu Li.
      Through millennia of evolution, some organisms can change colors rapidly for camouflage, communication, attraction, and warning to adapt to the dynamic environment. By mimicking the dynamic coloration strategies of natural organisms, artificial materials with responsive structural colors have emerged as promising candidates due to their environmental friendliness, real-time responsiveness to stimuli, and wide color gamut. These materials have attracted immense interest in anti-counterfeiting, displays, sensing, and smart actuators. This paper aims to present a survey on the response mechanisms, color modulation strategies, and applications of the structural color materials that are developed from different principles, such as photonic crystals (PCs), liquid crystals (LCs), and metasurfaces. We first discussed various structural color materials and their colorization mechanisms. We then classified these materials according to their color regulation strategies, such as responsiveness to physical, chemical, and biological stimuli. Subsequently, we provided a comprehensive overview of their applications for anti-counterfeiting, display technologies, sensing devices and detection platforms, and the biomedical field. Finally, we discuss the future prospects of responsive structural color materials and the issues that need to be addressed for their improvement. This review not only summarizes modulation strategies for dynamic structural colors but also provides valuable references and insights for future research in the field of structural coloration.
    Keywords:  bioinspired; dynamic; liquid crystal; metasurface; photonic crystal; structural color
    DOI:  https://doi.org/10.1021/polymscitech.5c00037
  41. ACS Biomater Sci Eng. 2026 Jun 12.
    Domain Coordination Governs Pore Architecture in Transient Double-Network Antibody-Binding Polyprotein Hydrogels.
    Sanam Bista, M A Mohaiminul Islam, Ionel Popa.
      Protein-based hydrogels synthesized from covalently cross- linked globular proteins are an emerging class of biomaterials, yet their dense nanoscale network architecture severely limits permeability to large biomolecules. Here, we report a general strategy to create highly permeable polyprotein hydrogels by photochemically cross-linking engineered octameric repeats of antibody-binding Protein A or Protein L in the presence of a transient alginate network, which can function as high-capacity affinity matrices. We demonstrate that the coordination capacity per domain controls the cross-linked shell that forms around growing pores during competitive gelation, with higher coordination (Protein L) producing a denser shell and more numerous but smaller pores and lower coordination (Protein A) yielding larger pores. The resulting hydrogels enable rapid and deep penetration of antibodies throughout the entire material volume while retaining high functional-domain density. When used as model affinity matrices, these materials display exceptional binding capacity, near-quantitative recovery, and excellent operational and shelf stability. This work establishes a molecular design rule for tuning porosity in folded-protein biomaterials and opens a route to next-generation, fully protein-based scaffolds with programmable permeability and function.
    Keywords:  affinity biomaterials; antibody purification columns; coordination-controlled porosity; photochemical cross-linking; protein-based hydrogels; transient double-network
    DOI:  https://doi.org/10.1021/acsbiomaterials.6c00634
  42. Langmuir. 2026 Jun 08.
    From Colloids to Hydrogels: Concentration-Dependent Cytocompatibility of Carboxylated Cellulose Nanocrystals Prepared via Deep Eutectic Solvents.
    Raúl Ortega-Córdova, Griselda Blanco-Gutiérrez, Priscila Quiñonez-Angulo, Francisco J Flores-Ruiz, Kaori Sánchez-Carrillo, J Félix Armando Soltero-Martínez, María G Pérez-García, Karla Juarez-Moreno, Josué D Mota-Morales.
      Cellulose nanocrystals (CNCs) are promising sustainable nanomaterials, yet their application in biointerfaces is often limited by fixed surface chemistries and limited insight into their concentration-dependent behavior. Here, we report a green and scalable strategy for CNC surface reprogramming using an oxalic acid-choline chloride deep eutectic solvent (ChCl-OAD DES), enabling controlled substitution of sulfate groups with carboxyl functionalities under mild conditions. The resulting carboxylated CNCs (CNC-COOH) preserve crystallinity and morphology while achieving tunable surface charge densities (up to ∼0.19 mequiv g-1) and improved thermal stability. We systematically investigate two distinct concentration regimes: dilute dispersions below 0.4 wt %, where CNC-COOH behaves as stable colloids, and concentrated systems at 2 wt %, where percolated hydrogel networks are formed. This transition is governed by hydrogen bonding and ionic screening, leading to pronounced changes in nanoscale organization and viscoelastic behavior. In biologically relevant media, CNC-COOH forms soft, elastic hydrogels (G' ≈ 102 Pa) capable of supporting three-dimensional (3D) cell encapsulation. Importantly, cytocompatibility is strongly dependent on material state. In the colloidal regime (<0.4 wt %), CNC-COOH exhibits negligible cytotoxicity toward 3T3-L1 fibroblasts and weak to mild cytotoxic effects toward HT-29 epithelial cells. In contrast, hydrogel networks (2 wt %) promote high cell viability (>85-100%) and enable 3D cellular organization. Protein adsorption appears to be limited at the surface of the CNC-COOH hydrogel, as indicated by BSA studies, suggesting that ionic strength-mediated interactions play an important role in network formation under cell culture conditions. These findings establish direct correlations among sustainable surface modification, concentration-dependent assembly, and biological response, providing design principles for CNC-based nanomaterials in biointerfaces, 3D cell culture, and nanomedicine.
    DOI:  https://doi.org/10.1021/acs.langmuir.6c02021
  43. Adv Sci (Weinh). 2026 Jun 09. e76015
    Beyond Molecular Determinism: State-Convergent Polymerization as a Functional Design Principle Under Chemical Complexity.
    Seonki Hong.
      Polymeric materials are traditionally designed by prescribing molecular structures and reaction pathways. However, many functional polymers-exemplified by natural melanins and synthetic polydopamine-operate reproducibly despite persistent molecular heterogeneity and ill-defined architectures. Here, I propose state-convergent polymerization (SCP) as a design logic for polymeric materials formed under chemical complexity, in which polymerization is defined by convergence toward a functional material state rather than a discrete molecular structure. In SCP, polymer formation emerges from dynamically evolving pools of reactive motifs confined within environmentally bounded chemical state spaces. Crucially, these state spaces are chemically addressable through experimentally accessible variables such as pH, redox conditions, oxygen availability, and interfacial confinement, enabling multiple reaction trajectories to coexist while enforcing functional convergence. By decoupling polymer function from molecular determinism, SCP provides a materials design framework for materials operating under chemical complexity, including biointerfaces, adaptive coatings, and open-system polymerization processes. This perspective reframes polymer synthesis from structure prescription toward state engineering, offering actionable principles for designing robust functional materials beyond molecular precision.
    Keywords:  functional state convergence; melanin‐inspired polymerization; polydopamine; state‐convergent polymerization; structural heterogeneity
    DOI:  https://doi.org/10.1002/advs.76015
  44. Cell Stem Cell. 2026 Jun 09. pii: S1934-5909(26)00227-4. [Epub ahead of print]
    SPACE-seq integrates spatial transcriptomics and lineage tracing in native tissues.
    Yuemeng Jia, Dawei Sun, Jackson A Weir, Xugeng Liu, Andrew J C Russell, YeEun Kim, Nicholas Thom, Giovanni Marrero, Vipin Kumar, Fei Chen, Fernando D Camargo.
      Understanding how cells change state, interact with their neighbors, and organize into tissues requires recording of cellular lineage history in native spatial context. Here, we present SPACE-seq (spatial tracing enabled by CRISPR-based barcodes and slide-seq), a versatile platform that integrates CRISPR-based lineage recording with spatial transcriptomics to jointly resolve lineage, cell state, and tissue architecture at near-cellular resolution in situ. Using SPACE-seq, we uncovered intratumor transcriptional diversification among clonally related cells and identified tumor-stroma crosstalk that reciprocally reshapes behaviors of both malignant and stromal populations, which we further experimentally validated. Beyond disease, SPACE-seq revealed a narrow developmental window in which hepatoblast dispersion contributes to spatially confined lineage compartments that prefigure liver lobar architecture. Together, these results highlight the broad applicability and adaptability of SPACE-seq to uncover previously inaccessible principles of cellular organization, lineage dynamics, and tissue patterning.
    Keywords:  brain development; cellular barcoding; lineage tracing; liver cancer; liver development; spatial transcriptomics
    DOI:  https://doi.org/10.1016/j.stem.2026.05.017
  45. Nat Commun. 2026 Jun 10.
    SciPhy: A Bayesian phylogenetic framework using sequential genetic lineage tracing data.
    Sophie Seidel, Antoine Zwaans, Samuel Regalado, Junhong Choi, Jay Shendure, Tanja Stadler.
      CRISPR-based lineage tracing offers a promising avenue to decipher single-cell lineage trees, especially in organisms not amenable to microscopy. Sequential genome editing records not only genetic edits but also the order in which they occur. To leverage this enriched information, we introduce SciPhy, a simulation and inference tool implemented in BEAST 2. SciPhy utilizes a Bayesian phylogenetic approach to jointly estimate time-scaled phylogenies and cell population parameters. After validation on simulated data, we use simulated and real data from a monoclonal cell culture to benchmark SciPhy against existing methods and find that it consistently reconstructs more accurate phylogenies. Compared to UPGMA, SciPhy additionally reports uncertainty and proliferation rates. Our second example applies SciPhy to murine gastruloids, demonstrating its ability to model time-varying population dynamics in early development. Together, these results establish a phylodynamic framework for the quantitative analysis of lineage tracing data. SciPhy's codebase is publicly available at https://github.com/azwaans/SciPhy.
    DOI:  https://doi.org/10.1038/s41467-026-73377-6
  46. Res Sq. 2026 Jun 03. pii: rs.3.rs-9310069. [Epub ahead of print]
    A Single-Cell Bioprinting Method to Reconstruct Native Cellular Microenvironments with Subcellular Resolution.
    Luiz Bertassoni, Haylie Helms, Kody Oyama, Ellen Langer, Alexander Davies.
      Tissue development and function are determined by the spatial organization of individual cells and their interactions. Yet experimental platforms capable of reconstructing cellular organization with single-cell precision for systematic interrogation remain lacking. Here we introduce a single-cell bioprinting platform that enables programmable reconstruction of cellular microenvironments through controlled single-cell placement with down to subcellular spatial control. We demonstrate intercellular spacing down to 1.3 µm, multiplexed deposition of up to eight cell types within a single construct, and reconstruction of biopsy-derived native cellular organization with 99% accuracy for single-cell placement relative to their native tissue coordinates. Using this framework, we show that manipulation of cellular arrangement allows for controlled interrogation of spatial transcriptional programs, cell-cell signaling networks, and migration dynamics in complex tissue microenvironments. This platform provides a generalizable experimental framework for causal interrogation of spatially defined cell-cell interactions at single-cell resolution.
    DOI:  https://doi.org/10.21203/rs.3.rs-9310069/v1
  47. Nat Protoc. 2026 Jun 10.
    Robust analytical methods for bis(monoacylglycero)phosphate profiling in health and disease.
    Wentao Dong, Kwamina Nyame, Eshaan S Rawat, Uche N Medoh, Jian Xiong, Caio C Bonin, Hisham N Alsohybe, Hunter Y Liu, Sara Gomes, Tammy Shalit, Marianna Arnold, Frank Hsieh, Esther Sammler, Monther Abu-Remaileh.
      Bis(monoacylglycero)phosphates (BMPs), a distinct class of anionic phospholipids predominantly found in late endosomes and lysosomes, plays a pivotal role in supporting lysosomal functions and maintaining metabolic homeostasis. Dysregulation of BMPs is associated with an array of disorders, notably neurodegenerative diseases. However, the identification and quantitation of BMP remains difficult because of its structural similarity to its isomer, phosphatidylglycerol (PG), thus necessitating robust analytical methods for accurate and reliable BMP profiling. In this study, we present comprehensive liquid chromatography (LC)-tandem mass spectrometry (MS2) methodologies for the precise and systematic analysis of BMP species in biological samples. We detail LC/MS methods for both an untargeted Orbitrap mass spectrometer and a targeted triple quadrupole mass spectrometer. We use differences in hydrophobicity and structure to annotate BMPs and PGs on the basis of retention time and positive-mode MS2 fragmentation patterns, respectively. Because genetic ablation of the BMP synthase CLN5 leads to specific depletion of BMPs but not PGs, lipid extracts from CLN5 knockout and wild-type cells can be compared to confidently annotate BMPs when MS2 data are incomplete. Lipid extraction and preparation of samples for LC/MS takes ~4 h, unattended LC/MS instrument time depends on the number of samples and computer-based data analysis takes ~1 d. Altogether, this approach constitutes a robust method for BMP profiling and annotation, furthering research into health and disease.
    DOI:  https://doi.org/10.1038/s41596-026-01379-1
  48. Nat Commun. 2026 Jun 10. pii: 4917. [Epub ahead of print]17(1):
    Synthesis of bundle copolymers as an emergent class of copolymer architecture.
    Yuki Kametani, Rintaro Yamaguchi, Yusuke Ando, Yuta Kawasaki, Takashi Uemura.
      Copolymers play a central role in soft materials owing to their capacity for diverse molecular designs. While numerous combinations of composition and topology have been explored for the development of copolymers, only four types of basic architecture (random, sequence-controlled, block, and graft) have been synthetically and historically achievable. Herein, we introduce an emergent class of copolymers, bundle copolymers, comprising multiple different chains interlinked and aligned in a parallel configuration. To exemplify this concept, bundle copolymers are synthesised via nanoconfined polymerisation, in which radical polymerisation of vinyl monomers occurs alongside vinyl-functionalised polydimethylsiloxane within the one-dimensional channels of a metal-organic framework. Unlike conventional copolymers, bundle copolymers feature aligned lateral strands whose proximity can be modulated by the density of covalent junctions. This innovative approach for tying multiple chains opens an avenue for copolymer design, expanding the landscape of polymer chemistry.
    DOI:  https://doi.org/10.1038/s41467-026-73978-1
  49. Nucleic Acids Res. 2026 Jun 08. pii: gkag592. [Epub ahead of print]54(11):
    Enhancing small-molecule-mediated translational control through multivalent RNA aptamers.
    Hui-Ye Feng, Xiao-Jie Wu, Xiao-Hui Li, Yan Liu, Liang Xu, Xiwen Xing.
      The precise translational control of gene expression by small molecules through RNA-based switches holds considerable promise for both research and therapeutic developments. However, current high-performance RNA switches remain limited in adaptability, with strong responses typically constrained to a narrow set of specific ligand-aptamer pairs. To address this limitation, we introduce a robust and generalizable RNA platform based on a multivalent aptamer design, which significantly enhances ligand-responsive protein expression through alternative splicing regulation. We have demonstrated that the inherently weak aptamers, such as those for theophylline or tetracycline, can be dramatically improved through this multivalency circuit, elevating the induction levels from modest (<10-fold) to over 100-fold, an increase of more than an order of magnitude. Leveraging these improved switches, we achieve multiplex and orthogonal control over distinct protein outputs with these suboptimal aptamers. Furthermore, we implement precise manipulation of cellular phenotypes through the ligand-controlled expression of functional proteins, including the pro-apoptotic effector BAX and the adhesion protein E-cadherin. This work establishes a general and adaptable RNA platform for expanding the toolbox of small-molecule regulators of protein expression, with potential applications across synthetic biology and therapeutic applications.
    DOI:  https://doi.org/10.1093/nar/gkag592
  50. IEEE Pulse. 2026 Mar-Apr;17(2):17(2): 21-22
    BioPrinted Hearts.
    Janet Rae-Dupree.
      Researchers at Stanford University are midway through a five-year US ${\$}$ 26.4 million "moonshot" project to develop the foundational technologies needed to bioprint new hearts using patients' own cells. Collaborators from 15 Stanford labs-including bioengineers, computational experts, electrical and mechanical engineers, surgeons, biologists, stem cell researchers, and developmental biologists-are working toward transplanting a manufactured heart into a pig by 2028. They must clear numerous hurdles to create a living, beating heart from scratch. So far, they have managed to increase stem cell production to "organ scale" and have developed a novel new technology for printing tissues and their vascular structures within a semi-solid gel. They are now puzzling out how to resolve issues with supporting that bioprinted tissue through synthesized vascular trees. The team recently finished developing a novel 3-D printer that can make tissue as complex as a heart fast enough that the cells will survive the printing process long enough to be connected to support structures to keep the resulting organ alive.
    DOI:  https://doi.org/10.1109/MPULS.2026.3677946
  51. Appl Environ Microbiol. 2026 Jun 09. e0053226
    Optimized cumate toolkit for tunable protein expression during in vitro and in vivo studies of Burkholderia cenocepacia.
    Hamza Tahir, Kristian I Karlic, Godfrey Mwiti, Nichollas E Scott.
      Inducible gene expression is pivotal to dissect bacterial physiology and virulence mechanisms. Across the Burkholderia genus, a limited range of inducible systems currently exist that allow tight regulation. In this study, we engineer a set of cumate inducible vectors for use in Burkholderia cenocepacia that offer minimal basal expression and the ability to control B. cenocepacia gene expression in eukaryotic cells. Through mutagenesis-based studies of cumate circuits and the cumate regulator (CymR), we have generated an optimized cumate circuit (PCymRC/CymRGV) which allows the tight and tunable control of protein expression in B. cenocepacia, as assessed by fluorescent and protein O-linked glycosylation analysis. Using comparative proteomics, we find that cumate elicits discrete alterations within the B. cenocepacia proteome that are orthogonal to those seen in widely used rhamnose-based induction systems, supporting cumate induction as a complementary approach for protein expression in Burkholderia spp. Leveraging the cell permeability of cumate and the generation of CTX-based chromosomal integration vectors, we show that inducible control of protein expression is achievable during intracellular replication of B. cenocepacia. By controlling intracellular expression of O-linked protein glycosylation, we demonstrate that protein glycosylation contributes to optimal intracellular replication of B. cenocepacia. This work demonstrates that cumate inducible systems allow precise and tunable gene expression in Burkholderia even within a host-pathogen context.IMPORTANCEThis work establishes optimized cumate-inducible vectors for use in Burkholderia cenocepacia, addressing the need for alternative inducers to available carbohydrate systems. We show that cumate-inducible vectors allow precise control of gene expression even within eukaryotic cells, providing a new and orthogonal way to temporally control protein induction. Utilizing cumate-based induction, we demonstrate the importance of O-linked protein glycosylation for optimal intracellular replication in B. cenocepacia, highlighting the potential of cumate systems to explore host-pathogen interactions. Combined, this work shows cumate-inducible vectors extend the range of studies which can be undertaken to dissect B. cenocepacia physiology and virulence.
    Keywords:  Burkholderia; Burkholderia cenocepacia; cumate induction; glycoproteomics; glycosylation; proteomics
    DOI:  https://doi.org/10.1128/aem.00532-26
  52. Sci Adv. 2026 Jun 12. 12(24): eaed9949
    Scalable hierarchical textile fibers toward personalized wearable atmospheric water harvesting.
    Chuxin Lei, Yongzheng Zhang, Lu He, Yuyang Wang, Juan Wu, Weixin Guan, Yaxuan Zhao, Qiang Fu, Keith P Johnston, Kai Wu, Guihua Yu.
      Sorption-based atmospheric water harvesting (AWH) offers a decentralized, sustainable solution to global freshwater scarcity, enabling clean water in diverse environments. However, translating ideal sorption properties of small-scale materials into practical, large-scale systems faces critical kinetic challenges. Here, we conceptualize a hierarchical textile fiber for wearable AWH, addressing the scaling limitations of traditional sorbents. These fibers feature an open-pore surface topology and internal hierarchical pore structures, which accelerate surface vapor liquefaction and subsequent water transport, demonstrating exceptional water uptake and rapid sorption kinetics across varying relative humidity (RH). When woven into textiles, the fibers maintain efficient vapor diffusion through their macroporous, breathable architecture, achieving a 3- to 10-fold improvement over traditional sorbents at scale. We engineered a wearable prototype combining the AWH textile with a portable collector, achieving 3.76 to 7.45 literswater per kilogramsorbent per day and collecting 410 to 894 milliliters across 20 to 80% RH. By overcoming kinetic limitations, our study advances AWH toward scalability and wearability with implications for global water sustainability.
    DOI:  https://doi.org/10.1126/sciadv.aed9949
  53. iScience. 2026 Jun 19. 29(6): 116132
    Stepwise multi-gate control of the HOG MAPK pathway under hyperosmotic stress.
    Kazuo Tatebayashi, Haruo Saito.
      In the budding yeast Saccharomyces cerevisiae, adaptation to hyperosmotic stress is mediated by the Hog1 mitogen-activated protein kinase (MAPK) via the high-osmolarity glycerol (HOG) pathway, which comprises a MAPK cascade and two upstream branches, SHO1 and SLN1. In the SHO1 branch, hyperosmotic stress is detected by transmembrane proteins such as Sho1, Opy2, Hkr1, and Msb2; however, the signaling steps directly controlled by the stress have remained unclear. Here, we show that hyperosmotic stress regulates three distinct steps within the SHO1 branch. It promotes the phosphorylation of the MAP2K Pbs2 by the MAP3K Ste11 through Sho1-dependent protein interactions and requires Hkr1, and it also regulates an upstream step required for Ste11 activation that depends on Hkr1 and Opy2. Together with a previously described step in Pbs2-mediated Hog1 phosphorylation, these findings show that osmotic stress regulates the pathway at three levels, defining stepwise multi-gate control of HOG pathway activation.
    Keywords:  Cell biology; Molecular biology
    DOI:  https://doi.org/10.1016/j.isci.2026.116132
  54. bioRxiv. 2026 Jun 02. pii: 2026.05.29.728803. [Epub ahead of print]
    Tet Trim-Away: A conditional rapid protein degradation system for Tetrahymena thermophila.
    Gayatri L Dholakia, Alexander J Stemm-Wolf, Aaisha Anzar, Aaron P Turkewitz, Chad G Pearson.
      Tetrahymena thermophila is a ciliated protist that has played pivotal roles in biological discovery. Functional studies of Tetrahymena proteins have largely relied on gene knockouts. Because protein depletion upon knockout typically spans multiple cell cycles, compensatory mechanisms can confound phenotypic interpretation. To instead enable rapid and acute protein depletion, we modified and adapted the Trim-Away system for use in Tetrahymena (Tet Trim-Away). Trim-Away is based on the E3 ubiquitin ligase, TRIM21, that binds to antibody-bound proteins and targets them for proteasome mediated degradation. Here, Trim-Away was modified with a fusion of the N-terminal RBCC (RING, B-box, coiled-coil) domains of TRIM21 with an α-mCherry (mCh) nanobody sequence that recognizes endogenously tagged mCh proteins of interest (Nb mCh ). Expression of the RBCC:Nb mCh degron, which is controlled by an inducible promotor, promotes rapid target protein depletion within 30 minutes and can be sustained for weeks. Tet Trim-Away is reversible, functions against targets in multiple cellular compartments, and produces loss-of-function phenotypes in Tetrahymena cells.
    DOI:  https://doi.org/10.64898/2026.05.29.728803
  55. Cell Rep. 2026 Jun 09. pii: S2211-1247(26)00588-7. [Epub ahead of print]45(6): 117510
    Peptide-MHC-targeted engineered virus-like particles enable selective priming and gene editing of tumor-specific T cells.
    Brian H Shim, Q Henry Zhao, Jack A Queenan, Blake E Smith, Michael E Birnbaum, David R Liu.
      Tumor-infiltrating lymphocyte (TIL) therapies harness tumor-specific T cells endogenous to a patient's repertoire but their efficacy is limited by challenges such as low frequencies of tumor-specific clonotypes and dysfunctional T cell phenotypes. These challenges necessitate technologies to engineer and reprogram endogenous tumor-specific TILs ex vivo. Here, we present a strategy using engineered virus-like particles (eVLPs) pseudotyped with peptide-major histocompatibility complexes (pMHCs) as a programmable, single-effector platform for selective and coordinated priming, expansion, and genome editing of rare antigen-specific CD8+ T cells among their endogenous polyclonal repertoires. We demonstrate that pMHC-pseudotyped eVLPs (pMHC-eVLPs) deliver T cell function-enhancing base editors to arm polyclonal lymphocytes with enhanced anti-tumor cytotoxicity by selectively expanding and engineering the tumor-specific T cell compartment. Our work establishes pMHC-eVLPs as a platform for enhancing TIL therapy with precision gene edits without the risks of bystander T cell engineering associated with polyclonal TIL engineering approaches.
    Keywords:  CP: cancer; TIL therapy; gene editing; genomics; targeted delivery; virus-like particles
    DOI:  https://doi.org/10.1016/j.celrep.2026.117510
  56. Chem Sci. 2026 May 29.
    Synthesis and applications of 1D and 2D nanoparticles prepared through crystallisation-driven self-assembly.
    Kaixiang Yang, Maria C Arno.
      Controlled, hierarchical assembly across length scales is a hallmark of natural materials and is often cited as the origin of their desirable properties - bone is the archetypal example, with its impressive combination of stiffness and toughness. Chemists have become adept at manipulating molecules, so it is now a fundamental goal of materials science to achieve a similar level of control over shape and size at the next level up: the nanoscale. This goal is now beginning to be realised, enabled by advances in precision polymer self-assembly methodologies. Crystallisation-driven self-assembly (CDSA) has emerged as a powerful technique to achieve nanoparticles of controlled morphology and size, which chemistry can be manipulated to achieve tuneable properties. In this perspective, we highlight the different methods for the CDSA of anisotropic nanoparticles (1D and 2D) with exquisite control over morphology and dimensions. We discuss the properties of these materials in a variety of different areas, from optoelectronics and information storage to biological processing and materials engineering, illustrating how nanoparticle chemistry can be modulated through living CDSA to produce nanomaterials with unique functionalities.
    DOI:  https://doi.org/10.1039/d6sc01312k
  57. Nat Commun. 2026 Jun 06.
    A nanoscale Jitterbug transformer from DNA.
    Seongmin Seo, Alexander A Swett, Mallikarjuna Reddy Kesama, Anirudh S Madhvacharyula, Ruixin Li, Yancheng Du, Markus Eder, Friedrich C Simmel, Jong Hyun Choi.
      Many viruses have evolved remarkably intricate polyhedral shells capable of undergoing symmetric transformations in response to external stimuli to initiate payload release. So far, such deployable auxetic nanostructures are not available in the synthetic realm. Here we present a nanoscale Jitterbug transformer realized by a DNA origami structure that can reconfigure its conformation upon chemical and optical signals while maintaining a Poisson's ratio of -1. By combining mechanical design principles with molecular dynamics simulations, we design the DNA Jitterbug to form a compact octahedron that stores elastic energy and spontaneously transitions into an expanded cuboctahedron by releasing it. DNA transformers are demonstrated to act similar to viruses that can create nanopores on lipid membranes and regulate payload release into vesicles. Integrating programmable DNA self-assembly with free-energy-guided mechanical design, this work provides a pathway toward adaptive nanomaterials with potential in synthetic organelles and stimuli-responsive nanodevices.
    DOI:  https://doi.org/10.1038/s41467-026-74070-4
  58. Nat Methods. 2026 Jun 09.
    Spatially resolved m6A profiling using m6A-ARTR-DBiT.
    Yu Xiao, Zhiliang Bai, Zhuoning Zou, Chang Ye, Bo Tao, Zhong Zheng, Yan-Ming Chen, Zhongyu Zou, Liudan Jiang, Lijie Zhao, Yuhang Fan, Yun Gao, Rong Fan, Chuan He.
      N6-methyladenosine (m6A) on RNA plays diverse regulatory roles, yet its spatial distribution within tissues remains largely unexplored. Here we introduce m6A-ARTR-DBiT, a spatial m6A profiling assay that leverages reverse-transcription-based detection and deterministic barcoding in tissue to map transcriptome-wide m6A distribution while preserving native tissue context. Applying m6A-ARTR-DBiT to mouse embryonic tissues and adult brains generates spatially resolved m6A landscapes and reveals region-associated m6A features across different functional domains. Pairwise comparison of spatial m6A profiles with spatial transcriptomes uncovers positive correlations between m6A levels and the expression of its methyltransferases and binding proteins, which also enables systematic identification of tissue-region-specific epitranscriptomic regulation. In the mouse hippocampus, m6A-ARTR-DBiT allows for high-resolution mapping of m6A organization within fine-scale tissue structures. Together, m6A-ARTR-DBiT provides a platform for interrogating RNA modification distribution within intact tissue sections, offering insights into the link between spatially patterned m6A deposition and gene regulation.
    DOI:  https://doi.org/10.1038/s41592-026-03123-9
  59. J Am Chem Soc. 2026 Jun 10.
    Total Synthesis of Conjugation-Ready Sulfated Red Algae Carrageenan Oligosaccharides for Sensing Applications.
    Yonatan Sukhran, Roey G Meir, Israel Alshanski, Shlomo Yitzchaik, Mattan Hurevich.
      Carrageenans are versatile sulfated marine galactans that possess attractive modification-dependent bulk properties, making them prime candidates for various cosmetic, drug delivery, and food-related applications. The structural diversity and intrinsic complexity of carrageenans hamper access to homogeneous polysaccharides, limiting the development of many carrageenan-based applications. We devised a synthetic strategy for the acquisition of a panel of γ-carrageenan-derived oligosaccharides with varying sulfation profiles and chain length. To that end, we synthesized a set of specialized building blocks with an elaborate multilevel protecting group hierarchy, tailor-made to specifically accommodate the structural complexity of carrageenans. In doing so, we uncovered interdependent protecting group and reactivity constraints, which we resolved strategically to adapt the synthetic route across the panel of carrageenans and minimize trade-offs. Assembly of di-, tri-, and tetrasaccharides with precise control over monomer connectivity and regiodefined sulfation on a conjugation-ready linker showcased the first total synthesis of homogeneous carrageenan oligogalactans. We demonstrated that the application of the curated panel enabled elucidation of the effect of γ-carrageenan molecular features on IL-8 binding preferences via electrochemical sensing and surface analyses.
    DOI:  https://doi.org/10.1021/jacs.6c09827
  60. ACS Appl Mater Interfaces. 2026 Jun 08.
    Programmable MOF-CNC Nanohybrid Networks Enabling Ion Transport Sensing and Efficient Water Purification.
    Hossein Ipakchi, Raymond X R Zhang, Tizazu H Mekonnen.
      The development of processable adsorbent materials that combine high capacity, fast transport, and structural stability remains a key challenge for water treatment applications. Here, a dispersible ZIF-cellulose nanocrystal (ZIF-CNC) nanohybrid platform is introduced and integrated within a poly(vinyl alcohol)-carboxymethylcellulose (PVA-CMC) matrix to form architecture-tunable materials with controlled transport properties. The nanohybrid enables uniform dispersion of ZIF-8 domains while preserving accessible porosity and interfacial functionality. By varying processing routes, the same composition is reconfigured into hydrogels and cryogels, allowing decoupling of composition from structure. In the hydrogel state, NaCl conditioning promotes ion enrichment and high ionic conductivity (up to 8.3 S·m-1), while in the cryogel state, freeze casting generates a highly porous and interconnected architecture (91% porosity, 0.14 g·cm-3 density) that enhances mass transport. The freeze-cast cryogel exhibits superior adsorption performance, achieving 97.6% removal of methylene blue and a maximum Cu2+ adsorption capacity of 154.5 mg·g-1 with 89.6% removal efficiency. Adsorption follows pseudo-second-order kinetics (R2 = 0.999) and is dominated by coordination and interfacial interactions at ZIF-CNC domains. The improved pore connectivity and accessibility in freeze-cast structures reduce mass transfer limitations and enhance utilization of active sites. Practical applicability is demonstrated through seed germination assays, where treated water restores plant growth to near-reference conditions. This work highlights a scalable strategy for coupling MOF nanohybrids with architecture-directed processing to control transport and adsorption performance, providing a versatile platform for high-efficiency water treatment.
    Keywords:  MOF─polymer composites; ZIF−CNC nanohybrids; ion adsorption; mass transport and porosity; water treatment
    DOI:  https://doi.org/10.1021/acsami.6c06849
  61. Carbohydr Polym. 2026 Sep 01. pii: S0144-8617(26)00566-7. [Epub ahead of print]387 125449
    Sustainable functionalization of natural polysaccharides via multicomponent reactions: Designs, properties, and applications.
    Fang Peng, Haisong Qi.
      The sustainable functionalization of natural polysaccharides is essential for expanding their advanced applications. Multicomponent reactions (MCRs) have emerged as efficient and environmentally friendly strategies for polysaccharide modification, offering high atom economy, modular functional-group installation, and operational simplicity. Although often considered green, the sustainability of MCR-based modification depends on the specific reaction system, including solvent choice, reagent hazards, and the targeted degree of substitution. In polysaccharide chemistry, MCRs can be conducted under homogeneous conditions with soluble derivatives or under heterogeneous conditions with insoluble substrates. These reactions enable the incorporation of diverse functional motifs, resulting in materials with tailored luminescence, UV shielding, antimicrobial and antiviral activity, amphiphilicity, hydrophobicity, enhanced water absorption, metal ion adsorption, and stimuli-responsiveness. This review summarizes recent advancements in the functionalization of natural polysaccharides through representative MCRs. The discussion focuses on reaction design principles, properties, and potential applications. Current challenges and future opportunities for polysaccharide functionalization via MCRs are also highlighted. We aim to offer insights for the development of advanced polysaccharide-based materials and to inspire innovative strategies for high-value utilization of natural polysaccharides.
    Keywords:  Functional materials; Hantzsch/Biginelli; Isocyanide; Mannich; Passerini/Ugi; Polysaccharide aldehyde/acetoacetate
    DOI:  https://doi.org/10.1016/j.carbpol.2026.125449
  62. Polym Sci Technol. 2026 Apr 28. 2(4): 222-247
    High Entanglement in Hydrogels: From Polymer Physics to Robust Mechanics.
    Yan Zhang, Hui Lou, Chunlei Yan, Qian Zhang, Yafei Wang, Yongjun Zhang.
      Entangled hydrogels offer a strategy to address the mechanical limitations of swollen networks, including conflicts between stiffness and toughness and between water content and robustness. In these systems, dense topological constraints generated by chain interpenetration act as dynamic crosslinks that complement covalent junctions, promoting stress transfer, recoverable energy dissipation, and improved fatigue and anti-swelling performance. This review first outlines the polymer-physics basis of entanglement, emphasizing tube and reptation concepts, entanglement molecular weight, and entanglement density, and the respective contributions of chemical crosslinks and entanglements to the elasticity of hydrogels. It then analyzes key factors governing the degree and stability of entanglement, including concentration, architecture and flexibility of chains, solvent conditions, and processing history. Experimental methods for probing entangled networks are summarized, covering mechanical and rheological testing together with scattering, imaging, and spectroscopic techniques that access structure and dynamics over different length and time scales. The role of entanglement in the design of robust hydrogels is discussed, highlighting how linking polymer-physics descriptors to network design has enabled robust performance in applications such as wound repair and adhesive biomedical patches, high-deformation flexible sensors, hydrogel electrolytes for energy devices, and mechanically stable environmental remediation materials. Finally, the review highlights current challenges associated with swollen-state entanglement physics, long-term durability and environmental stability, and quantitative structure-property relationships needed for predictable design and control of entangled hydrogel networks.
    Keywords:  chain entanglement; entangled hydrogel; mechanical properties; rheology; swollen polymer networks; topological constraint
    DOI:  https://doi.org/10.1021/polymscitech.6c00001
  63. Biofabrication. 2026 Jun 09.
    3D printed trichome-inspired permeable bioadhesive for wearable bioelectronics.
    Zhen Gu, Jingwen Xu, Heng An, Zhichao Dong, Xinhuan Wang, Yongqiang Wen, Qi Gu.
      Wearable bioelectronics that adhere directly to the skin have broad applications. However, achieving optimal breathability remains a significant challenge because of sweat accumulation at the device-skin interface. Conventional approaches, such as porous structures, often limit the functional versatility of wearable bioelectronics. To address this gap, we propose a sweat-removable skin sticker (SRSS) with a hierarchical trichome-inspired channel architecture that rapidly removes sweat from the interface while maintaining robust skin adhesion. The SRSS was fabricated through a hybrid process, in which the trichome-inspired hierarchical microchannel architecture was created by direct ink writing (DIW), enabling the controlled deposition of viscous ink with high structural fidelity. Through the multi-level ribs design, the SRSS demonstrated an effective area-normalized horizontal water removal rate (25.6 ml/cm²/min) significantly higher than the human sweat secretion rate (0.38-2.85 × 10⁻³ ml/cm²/min)-approximately three orders of magnitude. This feature reduces sweat accumulation in wearable bioelectronics, thereby enhancing user comfort. Unlike conventional porous materials, the SRSS relies on channel based adhesive interface design that remains compatible with attached wearable bioelectronics, such as temperature sensors in real time. This work therefore presents a structurally engineered permeable bioadhesive interface for wearable bioelectronics.
    Keywords:  3D printing; bioadhesive; bioelectronics; permeable; trichome-inspired
    DOI:  https://doi.org/10.1088/1758-5090/ae7b08
  64. ACS Synth Biol. 2026 Jun 11.
    Tunable and Orthogonal ECF and Anti-σ Threshold Gates for Temporal Control of Heterologous Gene Expression.
    Rebecca Wolters, Stefano Vecchione, Angelika Diehl, Georg Fritz.
      Precise timing of gene expression is a common feature in natural regulatory networks but is rarely implemented in synthetic pathways, where static control often limits performance. Here, we expand the use of bacterial extracytoplasmic function (ECF) σ factors by integrating their cognate anti-σ factors to create tunable threshold-gated circuits. Anti-σ overexpression has previously limited the utility of such systems due to growth inhibition. We address this by combining targeted truncations of membrane domains with chromosomal integration, yielding a library of ECF/anti-σ pairs that maintain function while minimizing toxicity. In Escherichia coli, these circuits can enable sharper OFF/ON switching, greater dynamic range, and tunable temporal delays compared with ECF-only cascades. In the best case, single-step threshold gates achieve up to 2100-fold induction with delays spanning minutes to hours. Extending the design to two steps enables programmable cascading of gene expression, with delays ranging from 30 to 409 min, although the dynamic range is generally reduced relative to single-step circuits. In the best-performing designs, matching input-output characteristics of promoters preserves dynamic range across cascade levels. Mathematical modeling supports these findings and highlights σ/anti-σ binding affinity as a key parameter for achieving high performance in longer cascades. Together, these results provide design principles for orthogonal, lower-burden timing circuits that enable controlled, sequential gene expression with minimal intervention in synthetic pathways and highlight continuing limitations of these systems.
    Keywords:  Antisigma sequestration; ECF sigma factors; Orthogonal regulation; Temporal gene expression; Threshold gates; Ultrasensitive switching
    DOI:  https://doi.org/10.1021/acssynbio.5c00799
  65. ACS Nano. 2026 Jun 11.
    Scalable Conformal Electronics Based on Roll-to-Roll Exfoliated van der Waals Semiconductors.
    Yigit Sozen, Esteban Zamora-Amo, Juan J Riquelme, Andres Castellanos-Gomez.
      Integrating electronic devices onto surfaces with complex topography such as skin, textiles, and biological tissues requires fabrication strategies that combine mechanical conformability with high electronic performance and scalable manufacturing. While two-dimensional (2D) semiconductors are promising materials for such applications, their integration into conformal electronic systems remains challenging because scalable liquid-phase processing typically yields films with limited electronic performance, whereas high-quality CVD materials require complex synthesis and transfer processes. Here, we establish a scalable route toward conformal electronics based on semiconducting van der Waals materials by combining high-throughput roll-to-roll mechanical exfoliation with commercially available temporary tattoo and waterslide decal transfer substrates. This approach enables the fabrication of ultrathin MoS2-based electronic devices that can be transferred onto rough and curved surfaces such as skin, synthetic leather, and plant leaves. The resulting devices operate reliably after transfer and exhibit strong electronic and optoelectronic performance, including photodetectors with responsivities up to ∼3.5 A W-1, thermistors with temperature coefficients of resistance of -2 to -3.5% °C-1, and ionic-gel-gated field-effect transistors with mobilities reaching ∼18 cm2 V-1 s-1.
    Keywords:  conformal electronics; field-effect transistors; molybdenum disulfide (MoS2); photodetectors; roll-to-roll exfoliation; tattoo electronics; thermistors
    DOI:  https://doi.org/10.1021/acsnano.6c04448
  66. J Phys Chem Lett. 2026 Jun 12.
    Inverted Potentials Enhance Electron Bifurcation Efficiency Prior to Steady State.
    Kiriko Terai, Abigail S Hjelmstad, David N Beratan.
      Electron bifurcation networks split electron pairs into strongly and weakly reducing pools at low thermodynamic cost. Bifurcating enzymes typically use two-electron cofactors with inverted reduction potentials. The advantages of inverted potentials remain unclear, as earlier studies on generic free energy landscapes showed that both normal and inverted potentials can support efficient steady-state bifurcation and confurcation. Here, we examine how potential inversion affects steady-state and pre-steady-state bifurcation and confurcation kinetics by modeling redox substrates as finite pools, to better represent finite biological systems. We confirm that both potential orderings support efficient steady-state bifurcation and confurcation. However, only inverted potentials suppress short-circuiting and reduce energy dissipation in the pre-steady-state regime of bifurcation and confurcation when the transport network is launched in an electron-depleted state. These findings suggest that when metabolism switches frequently between bifurcation and confurcation, where steady state is not maintained, inverted potentials at the bifurcating site confer an energetic advantage.
    DOI:  https://doi.org/10.1021/acs.jpclett.6c01292
  67. bioRxiv. 2026 Jun 05. pii: 2026.06.04.730180. [Epub ahead of print]
    A digital droplet microarray for measuring tolerance to antibiotics.
    Rena Fukuda, Nadia Nikulin, Shenghao Tan, Tobias Dörr, Nate J Cira.
      Antibiotic tolerance enables populations of microbes to survive normally lethal antibiotic concentrations, increasing the likelihood of reinfection and facilitating the evolution of resistance. Tolerance measurements typically involve quantifying viable cells after antibiotic exposure. Existing methods range from accessible but low-throughput approaches, such as plate counting, to higher-throughput but semi-quantitative techniques, such as the TDtest. Here, we develop a new system for rapid, precise and high-throughput tolerance measurements. We utilize Surface Patterned Omniphobic Tiles (SPOTs) to discretize cell suspensions into nano-to microliter droplets and estimate the viable cell concentrations following antibiotic exposure from the proportion of empty droplets using Poissonian statistics. We apply the platform to monitor Klebsiella pneumoniae tolerance to meropenem over time as a proof of concept. The resulting assay is accessible, compatible with multiple media, and boasts a large dynamic range, sufficient resolution, and rapid handling.
    DOI:  https://doi.org/10.64898/2026.06.04.730180
  68. PNAS Nexus. 2026 Jun;5(6): pgag167
    Searching for sequence features that control DNA cyclizability.
    Margarita Gordiychuk, Jonghan Park, Aakash Basu, Taekjip Ha, William Bialek, Yaojun Zhang.
      The mechanical properties of DNA molecules are crucial for many biological processes, from DNA packaging to transcription. While the mechanics of long DNA typically follow the worm-like chain polymer model, multiple studies have shown that the mechanics of short DNA, at the length scale of DNA-protein interactions, depend strongly on their sequence content. Motivated by recent high-throughput measurements of sequence-dependent DNA cyclizability-the DNA's tendency to mechanically bend and form a loop-we developed a statistical-mechanics framework to systematically explore how cyclizability depends on the collective contributions of an increasing number of nucleotides in the sequence. By applying the method to datasets of randomly generated and biologically derived sequences, we identified a minimal pairwise model that describes the sequence-dependence of DNA cyclizability. The pairwise model enabled the extraction of characteristic sequence features that control DNA cyclizability and predicted the most and least cyclizable sequences, which we validated through all-atom molecular dynamics simulations. Our work advances current understanding of sequence-dependent DNA mechanics and its role in various biological processes, with implications for the growing field of DNA nanofabrication.
    Keywords:  DNA cyclizability; sequence-dependent DNA mechanics; statistical-mechanics modeling
    DOI:  https://doi.org/10.1093/pnasnexus/pgag167
  69. ACS Appl Mater Interfaces. 2026 Jun 08.
    Programmable Nanoarchitectonics for Artificial Cells via Coupled Multidimensional Regulation of Phase State and Multiscale Transport Dynamics.
    Wenyan Lyu, Katsuhiko Ariga, Jingwen Song.
      The rational design of functional artificial cells is limited by the inherent thermodynamic instability and uncontrolled coalescence of the simple liquid condensates. Here, a programmable artificial cell platform is established based on the complex coacervation of bovine serum albumin and poly(acrylic acid). The physical state, mesoscale fusion dynamics, and multiscale mass-transport properties of these compartments can be tailored through the coupled multidimensional regulation of intrinsic polymer chain length, stoichiometric ratios, and environmental buffer conditions. Specifically, polymer chain length modulates condensate morphology and internal mobility, stoichiometric ratio tunes fusion kinetics and terminal size, buffer-mediated interactions promote wetting changes, condensate densification, and solid-like arrest. Crucially, combining spatiotemporal tracking and fluorescence recovery after photobleaching (FRAP) reveals a nonparallel relationship between internal network mobility and long-term molecular accumulation. More dynamic coacervate networks facilitate rapid internal mobility but show limited long-term accumulation, whereas densely packed, buffer-collapsed networks restrict internal diffusion yet exhibit favorable partitioning and affinity that support enhanced long-term cargo retention. By transforming fluidic microreactors into efficient "molecular traps," this study provides a versatile framework for smart biomaterials and artificial cell-like compartmentalization platforms.
    Keywords:  coacervate; diffusion; membraneless compartments; nanoarchitectonics; protein−polyelectrolyte interactions
    DOI:  https://doi.org/10.1021/acsami.6c06501
  70. Chem Sci. 2026 May 29.
    Grafting polymer brushes from nylon surfaces via hydrogen atom transfer.
    Tyler E Ball, Anna E Ringuette, Julianna R Koehl, Gozde Aktas Eken, Senthilkumar Duraivel, Christopher K Ober, Yadong Wang, Geoffrey W Coates, Brett P Fors.
      The direct functionalization of nylon surfaces with well-defined polymer brushes would enable access to functional materials for advanced biomedical and industrial applications. To this end, we developed a surface-initiated hydrogen atom transfer reversible addition-fragmentation chain-transfer (SI HAT-RAFT) polymerization to directly graft from nylon surfaces under mild conditions. Hydrogen abstraction by a triplet-excited thioxanthone catalyst initiates polymer chains, which are capped by a bistrithiocarbonate moiety. Our method is amenable to (meth)acrylic and acrylamide monomers and various commercially relevant nylon substrates, and we demonstrate spatial control over the polymerization by patterning nylon surfaces with polymer brushes. Finally, we explored the ability of our method to modify surface properties by measuring water contact angles with select polymer grafts and demonstrate that hydrophilic polymer brush modifications inhibit bovine serum albumin adsorption.
    DOI:  https://doi.org/10.1039/d6sc02508k
  71. Nat Commun. 2026 Jun 12.
    Engineering human PEG10-based nanoparticles for RNA self-packaging, delivery and cancer therapy.
    Pin-Yan Chen, Ting-Lun Tien, Vy Anh Truong, Quyen Thuc Dang, Nuong Thi Kieu Nguyen, Pin-Hsin Chen, Yu-Chen Hu.
      PEG10 protein was recently uncovered to self-assemble and self-package its own mRNA into nanoparticles, but the particles require expensive transfection for production and have yet to be explored for cancer therapy. Here we develop a human PEG10-based nanoparticles (PBNPs) platform for cargo RNA self-packaging and delivery for cancer therapy. We design a process to improve the PBNPs production for 11.3-fold while reducing the cost. The PBNPs self-package mRNA of at least 7336 nucleotides and remain stable for 7 months. We engineer the PBNPs surface and tremendously improve mRNA delivery efficiencies to various cancer cells, particularly colon cancer cells (≈71%). We further reprogram the PBNPs to deliver an immunotherapeutic mRNA cocktail to colon cancer cells, which elicits T cell responses in vitro. In vivo co-administration of the engineered PBNPs and chemodrug in female mice synergizes immune responses and promotes anti-cancer efficacy, implicating the potential of PBNPs as an RNA delivery vehicle for immunotherapy.
    DOI:  https://doi.org/10.1038/s41467-026-74352-x
  72. ACS Appl Mater Interfaces. 2026 Jun 09.
    Label-Free and In Situ Glycophenotyping Using a Glycocalyx-Mimetic Electrochemical Transducer.
    Thiago Coimbra Pimenta, Alexandre Xavier Mendes, Ronil J Rath, Luiza Aguiar do Nascimento, Vatsala Pithaih, Henry F F Bellette, Eliza Grills, Andreas Behren, Dênio E Pires Souto, George Wren Greene, Simon E Moulton, Jessica Da Gama Duarte, Saimon M Silva.
      Rapid glycophenotyping is often limited by biofouling, reliance on complex, multistep labeling, and poor access to living cell surfaces. Here, however, we introduce a glycocalyx-mimetic electrochemical interface that converts lectin-glycan binding into multiplex electrical signals. We coat gold electrodes with a self-assembled brush of lubricin (PRG4), whose densely O-glycosylated mucin domains present tumor-associated truncated O-glycans that serve as linkers to the lectins, our recognition elements. Embedding six lectins within lubricin enables orthogonal recognition of Gal-GalNAc-terminated oligosaccharides. In an electrochemical culture-plate format, the resulting sensor supports real-time, in situ glycophenotyping of melanoma cells, achieving quantitative agreement to a conventional, end point, lectin microarray. This glycocalyx-mimetic transducer thus enables the rapid, label-free screening of lectin-glycan interactions and the profiling of diagnostically relevant, tumor-associated glycans.
    Keywords:  electrochemical transducer; glycan detection; label-free screening; lectins; lubricin
    DOI:  https://doi.org/10.1021/acsami.6c04290
  73. Elife. 2026 Jun 10. pii: RP111544. [Epub ahead of print]15
    Cell size modulates ferroptosis susceptibility.
    Evgeny Zatulovskiy, Magdalena B Murray, Shuyuan Zhang, Scott J Dixon, Jan M Skotheim.
      Size is a fundamental property of cells that influences many aspects of their physiology. This is because cell size sets the scale for all subcellular components and drives changes in the composition of the proteome. Given that large and small cells differ in their biochemical composition, we hypothesized that they should also differ in how they respond to signals and make decisions. Here, we investigated how cell size affects the susceptibility of human cells to cell death. We found that large cells are more resistant to ferroptosis caused by system xc- inhibition. Ferroptosis is a type of cell death characterized by the iron-dependent accumulation of toxic lipid peroxides. This process is opposed by cysteine-dependent lipid peroxide detoxification mechanisms. We found that larger cells exhibit higher concentrations of the cysteine-containing metabolite glutathione and lower concentrations of membrane lipid peroxides. Mechanistically, this can be explained by the fact that larger cells had lower concentrations of an enzyme that enriches cellular membranes with peroxidation-prone polyunsaturated fatty acids, ACSL4, and increased concentrations of the glutathione-producing enzymes glutamate-cysteine ligase and glutathione synthetase, the iron-chelating protein ferritin, and the lysosomal protease cathepsin B, which can catabolize cysteine-rich extracellular proteins to produce additional cystine for fueling the synthesis of glutathione. Taken together, our results highlight the significant impact of cell size on cellular function and survival, revealing a size-dependent vulnerability to ferroptosis that could influence therapeutic strategies based on this cell death pathway.
    Keywords:  biochemistry; cell biology; cell death; cell size; chemical biology; erastin2; ferroptosis; glutathione; heterogeneous response; human; scaling
    DOI:  https://doi.org/10.7554/eLife.111544
  74. J Cell Sci. 2026 Jun 10. pii: jcs.264323. [Epub ahead of print]
    Apical-out polarity in epithelial spheroids requires α6β4 integrins, cell proliferation, and anchorage-independence.
    Niharika Patel, Jenna Pirrello, Skylar Lynch, Hailee Patel, Bradley J Sweeney, Shivam Priya, Tanmay P Lele, Aki Manninen, Daniel E Conway.
      Epithelial cells primarily segregate transmembrane proteins to apical or basal surfaces, establishing apical-basal polarity. For 3D tissues, apical proteins face inwards. Recent work by our group showed that increased RhoA activation causes epithelial spheroids to invert apical-basal polarity via a collective rearrangement of cells, a process we and others have termed eversion. In this work we determined that α6ß4-laminin interactions are required for spheroids to evert to apical-out polarity. Additionally, we show that increased cell proliferation and anchorage independence are required to sustain apical-out polarity. We also observed that apical-out spheroids can 'revert' to apical-in polarity through apoptotic cavitation of cells located in the center of the spheroids. This study provides new mechanistic insights into the biochemical and biophysical mechanisms that drive eversion and maintain apical-out polarity, and supports the concept that apical-basal polarity orientation may drive phenotypic switching of epithelia.
    Keywords:  Anchorage-independence; Apical-basal polarity; Integrins
    DOI:  https://doi.org/10.1242/jcs.264323
  75. bioRxiv. 2026 Jun 02. pii: 2026.06.01.729314. [Epub ahead of print]
    On the Distribution of Free-Energy in Metabolism.
    Ian Cook, Thomas S Leyh.
      Chemical potential is coupled to cellular processes by the flow of metabolites through catalytic networks known collectively as metabolism. Here we describe an extensive new class of energy-coupling catalysts that act to interconnect metabolic network pathways and their potentials. Members of the class are defined by a common mechanism - half-site reactivity. The well-established sequential subunit turnover of half-site enzymes suggests that the potentials of reactions occurring at the separate subunits are coupled to one another. Here this hypothesis is tested and validated using promiscuous half-site enzymes from two catalytically distinct enzyme families, each with broad metabolic penetrance. Fundamental catalytic parameters (V max and K m ) and reaction endpoints are predicted and shown to change dramatically when reaction potentials are coupled - for example, the catalytic efficiency (V max /K m ) and endpoint of the retinol oxidation reaction (the rate-limiting step in vitamin A synthesis) are shown to increase 900- and 3,400-fold, respectively, when the reaction is coupled to the more favorable oxidation of ethanol. For the first time it is clear that metabolism has the flexibility to react to changes in the metabolic state of the cell by redistributing chemical potential among the many metabolic pathways interconnected by half-site enzymes.
    Significance: The findings herein reveal the existence of an extensive, catalytically diverse network of enzymes that distributes chemical potential within and across the pathways of small-molecule metabolism. Members of the network are identified on the basis of a shared mechanistic trait - half-site reactivity. These energy-coupling catalysts allow reactions to proceed orders of magnitude further and more efficiently than their intrinsic potentials allow by coupling them to more favorable reactions. The work offers a raison d'etre for the half-site mechanism and powerful new strategies for de novo metabolic pathway design.
    DOI:  https://doi.org/10.64898/2026.06.01.729314
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