bims-enlima Biomed News
on Engineered living materials
Issue of 2026–07–05
sixty-six papers selected by
Rahul Kumar, Tallinna Tehnikaülikool
  1. Lipid Network Crosslinked Hydrogels: Controlling Material Dynamics Across Multiple Length Scales Through Lipid Movement.
  2. Programming Bio-Bio Electronic Interfaces for Light-Driven Interspecies Electron Transfer.
  3. Iterative Bump-and-Hole Engineering Creates a Bioorthogonal Reporter for N-Acetylglucosaminyltransferase I.
  4. Combinatorial decision-making driven by multicomponent surface condensates.
  5. Annotating the pangenome reveals the diversity in the genetic basis for metabolic enzymes.
  6. S-layers as natural building blocks for nanobiotechnology and synthetic biology.
  7. BODIPY Photocage-Based Injectable Hydrogel for Light-Controlled Nanoparticle Release.
  8. Unraveling Self-Assembly Mechanisms in Bacterial Cellulose Hydrogels.
  9. Bioinstructive Orthogonally-crosslinked Ovoprotein Microgels for Modular Bioprinting.
  10. Improving cell-free metabolism through direct integration of artificial respiratory chains.
  11. Bioinspired Regenerative Lignification Enables Ultra-Hard and Sustainable Bamboo Structural Materials.
  12. Bacterial spores as a modular platform for the production of amyloids for materials.
  13. Post-translational negative feedback loops are sufficient to coordinate synthesis of the gram-negative envelope during steady-state growth.
  14. Fiber-reinforced hydrogels: From multiscale structural design to advanced engineering applications.
  15. Artificial metalloenzymes in complex biological environments.
  16. A wireless subdural-contained brain-computer interface with 65,536 electrodes and 1,024 channels.
  17. Membrane protein solubilization and structure determination using de novo-designed proteins.
  18. Agnostic material classification using differential de Bruijn graphs of DNA imprints.
  19. Recyclable Photopolymers for Sustainable 3D Printing.
  20. Navigating the Forest of Lignin-Derived Monomers for Polymer Synthesis.
  21. High-precision memristor-based computing.
  22. Chemically Fueled Interfacial Supramolecular Polymerization.
  23. Floatony formation in liquid environments: liquid drawing-based fabrication of three-dimensional microbial structures.
  24. Unlocking the chemical potential of filamentous fungi using prime editing.
  25. High-throughput DNA engineering by mating bacteria.
  26. Solvent-Driven Biphasic Architectures in Polymer Gels via Polymerization-Induced Solvent Phase Separation.
  27. Spontaneous Helical Alignment of Smooth Muscle Cells to Form a Medial Layer for Engineered Microvasculature.
  28. Dissecting autonomous enzymatic variability in single cells.
  29. Lab creates new kind of synthetic cell.
  30. Large-area, photo-programmable 2D semiconductors with chromic molecular functionalization.
  31. Systematic design of auxotrophic strains and media conditions to probe metabolic functions in E. coli.
  32. 3D-Printed Milli-Fluidic Mixing-Extrusion Platform for Continuous, High-Throughput LNP Production.
  33. A data-driven modeling framework for mapping genotypes to synthetic microbial community functions.
  34. Bioorthogonally reinforced injectable granular hydrogels synergizing ECM mimicry with microporosity for skin tissue engineering.
  35. Toward autonomous robotic-assisted and microrobotic surgery.
  36. Spontaneous Phase Separation Enables Rapid, Polymerization-Free Fabrication of Gels.
  37. Engineering Layered Magnetic Hydrogels for Cell Placement via Shear and Magnetic Field-Induced Assembly.
  38. Cellular replisomes are powered by flex-fuel motors for unwinding DNA.
  39. High-throughput measurements of protein domain functions using magnetic separation.
  40. Inorganic biomaterials-reinforced printable hydrogel modulating regenerative microenvironments for tissue repair.
  41. Living bacterial reservoir computers for information processing and sensing.
  42. Engineering Modular Cargo Loading Strategies for Carboxysome-Derived Protein Particles.
  43. Dual-Modulus Microcone Array for Graded Tactile Sensing and Intelligent Slip Detection.
  44. Programming T cells for intercellular genome editing.
  45. Advancing synthetic biology with engineered chemically inducible gene regulatory systems.
  46. An open-source 3D printing system enabling in-situ freeze-thaw processing of hydrogels.
  47. Label-Free All-Electrical Tracking of Individual and Collective Cell Migration on a Megapixel CMOS Capacitance Sensor.
  48. Designing Thermally Stable DNA Hydrogels via Entropically-Driven Acridine Intercalation.
  49. Engineering Rhodotorula toruloides as a platform organism for de novo synthesis of fatty-acid esters.
  50. Beyond the 2D Plane: Interfacing Microwave Resonators with Bioreceptor-Functionalized Hydrogel Micropillars for Label-Free Enhanced Sensitivity Biosensing.
  51. Mitochondrial-generated G-quadruplex-forming lncRNAs regulate heme homeostasis.
  52. Enzymatically Polymerized Glycolated Conductive Polymers as Soft Electrodes for Neural Bioelectronic Interfaces.
  53. Photoregulated Structural Memory in Supramolecular Polymers.
  54. Particle-Only gECM Wafers Enable Cohesive, ECM-Rich Scaffolds Without Secondary Polymers.
  55. Impact-Resistant Hydrogels Via Quaternary Ammonium-Regulated Networks.
  56. Beyond unit cells: Programmable morphogenetic design of irregular architected materials.
  57. CREAT: A CRISPR-Based Genome Trimming Strategy for Systematic Identification of Dispensable Regions and Rapid Genome Reduction.
  58. Intracellular assembly of artificial enzymes for cytoplasmic enantioselective Mannich reactions.
  59. As transistors get smaller, electrodes must keep shrinking too.
  60. Composite Liquid Marble Templated Millimetric Capsule With Tunable Rigidity, Porosity, and Thermal Reconfigurability Toward 3D Cell Culture.
  61. A metabolon channels nicotine biosynthesis.
  62. Transcriptional regulatory network differences between six industrial Escherichia coli strains.
  63. Genome-wide absolute quantification of chromatin looping.
  64. Scalable enumeration and sampling of minimal metabolic pathways for organisms and communities.
  65. Programmable one-pot polymerase-mediated DNA synthesis via temperature control.
  66. Artificial intelligence for food innovation.
  1. bioRxiv. 2026 Jun 25. pii: 2026.06.24.734376. [Epub ahead of print]
    Lipid Network Crosslinked Hydrogels: Controlling Material Dynamics Across Multiple Length Scales Through Lipid Movement.
    Neil J Baugh, Michelle S Huang, Narelli de Paiva Narciso, Jordan A Bunch, Jayniana Williams, Yueming Liu, Ruby Onsongo, David Kilian, Renato S Navarro, Sarah C Heilshorn.
      Control over network dynamics at different length scales is a feature of natural materials challenging to replicate in synthetic hydrogels. Hydrogel viscoelasticity is commonly controlled by tuning the kinetics of reversible crosslinks; however, this strategy inherently links the resulting macroscale and nanoscale dynamics of the individual network components. Taking inspiration from biological materials that feature lipids as structural elements, we introduce Lipid Network Crosslinked (LINC) hydrogels that exploit the mobility of individual lipids within self-assembled liposomes as covalent, network-crosslinking points. These mobile, covalent crosslinks increase hydrogel stress relaxation rates over 20-fold compared to polymer-only hydrogels with equivalent crosslinking chemistries and stiffnesses. We demonstrate that liposome design parameters, including degree of surface functionalization and tail saturation, provide a means to independently control the macroscale storage moduli and stress relaxation behavior. Finally, as an application where control over network dynamics at different length scales is critical, we placed cell-adhesive ligands onto more mobile or less mobile network elements. Human neural progenitor cells cultured within LINC hydrogels of identical macroscale viscoelasticity significantly altered their phenotype in response to nanoscale ligand dynamics. These results establish LINC hydrogels as biomimetic materials that leverage nanoscale lipid mobility within a macroscale polymeric network to control dynamics at multiple length scales.
    DOI:  https://doi.org/10.64898/2026.06.24.734376
  2. Angew Chem Int Ed Engl. 2026 Jun 30. e8664414
    Programming Bio-Bio Electronic Interfaces for Light-Driven Interspecies Electron Transfer.
    Lancheng Wang, Peng Chen, Yujie Wang, Chi Hu.
      Living systems organize electron flow through continuous, spatially and energetically structured redox networks, whereas most synthetic light-driven bioelectronic platforms rely on abiotic materials to generate and inject electrons into cells, limiting selective coupling between living partners. Here, we report programmable living electronic interfaces that enable direct, light-driven interspecies electron transfer (IET) between two living microorganisms. A conformal poly(3,4-ethylenedioxythiophene) network integrated into the envelope of Synechococcus elongatus intercepts and relays photosynthetic electron flux, while supramolecular cucurbit[7]uril host-guest interactions program defined cell-cell assembly with engineered Escherichia coli. Redox-active mediators embedded within the interface establish energetically matched electron-transfer pathways across species boundaries. Redox-potential matching identifies neutral red as an optimal mediator, enabling selective delivery of photosynthetic electrons into E. coli with an IET efficiency of 83.7%, thereby enhancing light-driven biocatalysis. This work establishes an integrated bio-bio electronic architecture that embeds electronic conduction within living redox networks, defining a paradigm for constructing light-powered microbial consortia distinct from conventional abiotic-bio hybrid systems.
    Keywords:  conductive polymer; host–guest interaction; interspecies electron transfer; redox mediators; sustainable biocatalysis
    DOI:  https://doi.org/10.1002/anie.8664414
  3. J Am Chem Soc. 2026 Jun 30.
    Iterative Bump-and-Hole Engineering Creates a Bioorthogonal Reporter for N-Acetylglucosaminyltransferase I.
    Yu Liu, Saskia Pieters, Ganka Bineva-Todd, Mert Sagiroglugil, Sean A Burnap, Freya Hoddle, Anna Cioce, Andre Ohara, Sophie D Schmidt, Kevin Bruemmer, Carolyn R Bertozzi, Karen Polizzi, Weston B Struwe, Carme Rovira, Benjamin Schumann.
      Asparagine-linked protein glycosylation is among the most frequent modifications of proteins trafficking through the secretory pathway. These glycans are manufactured in an assembly line process, yielding a common precursor that is then subjected to individual modifications with different levels of complexity. An important biosynthetic modulator is the incorporation of N-acetylglucosamine (GlcNAc) at distinct positions in N-linked glycan biosynthesis, commencing with the activity of the glycosyltransferase MGAT1. While mapping of N-glycans to their corresponding protein attachment sites is generally possible, not much is known about the glycoprotein substrate choice for MGAT1 and related transferases. Analogs of GlcNAc with small bioorthogonal tags can be incorporated into N-glycans. However, due to the promiscuity of some GlcNAc transferases, incorporation is of little specificity toward individual positions. Here, we report an iterative bump-and-hole approach for the design of a bioorthogonal precision tool to study the activity of MGAT1 in mammalian cells. Structure-informed protein engineering abrogated the activity of MGAT1 toward the nucleotide-sugar UDP-GlcNAc while retaining activity toward bumped, azide-modified analogs. Kinetic and computational analyses using a neural network approach informed the synthesis of a tailored UDP-GlcNAc analog with preferential acceptance by the engineered enzyme. Following substrate biosynthesis, the strategy allowed selective incorporation of a chemical tag on MGAT1 substrate proteins in living mammalian cells with little background incorporation by other GlcNAc transferases. Our work expands the toolbox for glycan-based reporter compounds.
    DOI:  https://doi.org/10.1021/jacs.6c01114
  4. Proc Natl Acad Sci U S A. 2026 Jul 07. 123(27): e2527873123
    Combinatorial decision-making driven by multicomponent surface condensates.
    Aidan Zentner, Ethan V Halingstad, Cameron Chalk, Michael P Brenner, Arvind Murugan, Erik Winfree, Krishna Shrinivas.
      Living organisms rely on molecular networks, such as gene circuits and signaling pathways, for information processing and robust decision-making in crowded, noisy environments. Recent advances show that interacting biomolecules self-organize by phase transitions into coexisting spatial compartments called condensates, often on cellular surfaces such as chromatin and membranes. In this paper, we demonstrate that multicomponent fluids can be designed to recruit distinct condensates to surfaces with differing compositions, performing a form of surface classification by condensation. We draw an analogy to multidimensional classification in machine learning and explore how hidden species, analogous to hidden nodes, expand the expressivity and capacity of these interacting ensembles to facilitate complex decision boundaries. By simply changing levels of individual species, we find that the same molecular repertoire can be reprogrammed to solve new tasks. Together, our findings suggest that the physical processes underlying biomolecular condensates can encode and drive adaptive information processing beyond compartmentalization.
    Keywords:  biophysics; condensates; molecular computation; self-organization
    DOI:  https://doi.org/10.1073/pnas.2527873123
  5. Sci Adv. 2026 Jul 03. 12(27): eaeb3363
    Annotating the pangenome reveals the diversity in the genetic basis for metabolic enzymes.
    Omid Ardalani, Patrick V Phaneuf, Kalpathy J Krishnan, David Pride, Lars K Nielsen, Bernhard O Palsson.
      Affordable sequencing has flooded public databases with bacterial genomes; yet, species-scale maps that connect gene content variation to metabolic functions essential to biotechnology/system biology remain scarce. We address this gap by building a pangenome-wide gene-protein-reaction association and applying it to 2377 Escherichia coli genomes to reconstruct a pangenome-scale metabolic model (panGEM). We validate panGEM against Biolog carbon source utilization assays, achieving ≈0.99 precision in growth/no-growth predictions. Using panGEM, we identify >11,000 rare metabolic genes, yet only 35 metabolic reactions are rare. To explain the mismatch, we examined rare genes and found that most are pseudogenes or diverged orthologs acquired by horizontal gene transfer (HGT). Results indicate a recurrent loss-reacquisition cycle in which a core allele is lost/pseudogenized and its function is restored by HGT, preserving function without expanding the reactome, generating genetic heterogeneity in a small subset (~3.6%) of reactions, marking selection pressure hotspots of metabolism. Thus, pangenome annotation reveals the evolutionary dynamics that shape the genetic basis of metabolism.
    DOI:  https://doi.org/10.1126/sciadv.aeb3363
  6. Curr Opin Microbiol. 2026 Jul 03. pii: S1369-5274(26)00081-0. [Epub ahead of print]92 102787
    S-layers as natural building blocks for nanobiotechnology and synthetic biology.
    Uwe B Sleytr, Bernhard Schuster.
      Crystalline bacterial cell surface layers (S-layers) are self-assembling protein lattices that constitute the outermost envelope structure of many Bacteria and most Archaea. Beyond their classical role as cell surface components, S-layers are increasingly recognized as programmable, two-dimensional biological materials that combine nanometer-scale precision, defined porosity, and exceptional physicochemical properties. In this review, we synthesize current understanding of S-layer architecture, assembly, and functionalization to position them as a unifying platform for nanobiotechnology and synthetic biology. We highlight how their intrinsic self-assembly and genetic engineerability enable the design of ordered biomolecular interfaces with applications ranging from molecular sieving, biosensors, biomineralization, and nanoscale patterning. Engineered S-layer fusion proteins allow the modular and spatially controlled display of functional domains, bridging bottom-up materials design with biological complexity. Beyond their technological relevance, S-layers play underappreciated roles in host-microbe interactions, where their structural regularity and surface accessibility shape immunogenicity and cellular recognition, with implications for vaccine development, targeted delivery, and microbiome engineering. We argue that overcoming current limitations in scalable production, stability, and system integration will be key to unlocking the full potential of S-layers as genetically programmable, bio-inspired interfaces, enabling a new class of adaptive nanomaterials and advancing the design principles of synthetic biological systems.
    DOI:  https://doi.org/10.1016/j.mib.2026.102787
  7. Small. 2026 Jul 01. e74162
    BODIPY Photocage-Based Injectable Hydrogel for Light-Controlled Nanoparticle Release.
    Baihao Shao, David J Peeler, Thomas F F Fernandez Debets, Jonathan P Wojciechowski, Yue Shao, Yuxi Cheng, Kun Zhou, Robin J Shattock, Molly M Stevens.
      Light-controlled release of therapeutics holds great promise for improving patient compliance with treatment plans against many leading diseases and could contribute to a better quality of life for people suffering from chronic conditions. However, insufficient tissue penetration of light largely limits the in vivo applications of photoresponsive therapeutics. With the aim to circumvent this limitation and to work within tissue depths that are pragmatically accessible to light, we developed an injectable and photodegradable hydrogel that could enable controlled drug delivery in subcutaneous tissue. In this work, we describe a hydrogel formulation consisting of a 2-arm photocage bearing azide and a BCN-terminated 4-arm PEG. Gelation takes place in minutes upon mixing the two components via strain-promoted azide-alkyne cycloaddition (SPAAC). Both gel precursors are made water-soluble and exhibit low viscosity prior to complete gelation, and the pre-gel is easily injectable through 23G needles. Photocage photocleavage and consequent gel degradation could be precisely controlled with green light irradiation. We further showed that nanoparticles can be successfully encapsulated into the gel and subsequently photo-released. The full operation process was demonstrated in an ex vivo porcine model and the acute biocompatibility of gel injection and degradation was evaluated in healthy human skin cultured ex vivo.
    Keywords:  click chemistry; controlled release; injectable hydrogel; photocage
    DOI:  https://doi.org/10.1002/smll.74162
  8. Biomacromolecules. 2026 Jun 29.
    Unraveling Self-Assembly Mechanisms in Bacterial Cellulose Hydrogels.
    Go Takayama, Tetsuo Kondo.
      Bacterial cellulose (BC) hydrogels produced by Gluconacetobacter species hold considerable promise for a wide range of applications owing to their exceptional mechanical properties, biocompatibility, and biodegradability. Achieving precise control over their structural and mechanical characteristics is crucial for the engineering of BC-based materials. In this study, we investigated the formation dynamics and structural features of BC hydrogels, emphasizing the complex interplay between cellulose nanofibril secretion and bacterial motility. Comprehensive tracking of bacterial movement during hydrogel formation has validated mechanisms underlying the development of branching and merging junctions, which are key elements that define the network's physical properties. Additionally, we observed the emergence of vortex-lattice and chiral-nematic structures during hydrogel development, depending on bacterial and cellulose densities. These insights contribute to a fundamental understanding of bottom-up 3D fabrication of BC hydrogels that harness the collective behavior of cellulose-producing bacteria.
    DOI:  https://doi.org/10.1021/acs.biomac.5c02746
  9. bioRxiv. 2026 Jun 19. pii: 2026.06.17.732926. [Epub ahead of print]
    Bioinstructive Orthogonally-crosslinked Ovoprotein Microgels for Modular Bioprinting.
    Suihong Liu, Vaibhav Pal, Joseph Christakiran Moses, Medine Dogan Sarikaya, Deepak Gupta, Miji Yeo, Valeriya Stepanyants, Yasar Ozer Yilmaz, Ibrahim T Ozbolat.
      Bioprinting increasingly requires biomaterials that are not only printable, but structurally adaptive and biologically instructive. Here we establish an ovoprotein-derived microgel platform that couples intrinsic protein bioactivity with orthogonal interparticle photocrosslinking for modular bioprinting. Methacrylated ovoproteins yielded a photoresponsive protein-rich hydrogel matrix with retained proteomic complexity, tunable mechanics, and cell-regulatory biofunction. Endogenous tyrosine chemistry drove interparticle dityrosine coupling between ovoprotein microgels, producing cohesive, microporous, and intrinsically autofluorescent granular networks. The resulting systems displayed programmable rheology and broad compatibility across digital light processing, extrusion-based and aspiration-assisted bioprinting. Functionally, the ovoprotein microgel matrices attenuated sustained pro-inflammatory macrophage activation, promoted endothelial organization and host angiogenic invasion, and supported spheroid-mediated vascular morphogenesis with progressive sprouting, lumenization, branching and inosculation. It further enabled bioprinted osteogenic constructs with long-term maturation into bone-like mineralized tissues in vitro . These findings establish ovoprotein microgel-spheroid bioassembly as an adaptive, bioinstructive strategy for engineering vascularized and mineralized tissue constructs.
    DOI:  https://doi.org/10.64898/2026.06.17.732926
  10. Proc Natl Acad Sci U S A. 2026 Jul 07. 123(27): e2613483123
    Improving cell-free metabolism through direct integration of artificial respiratory chains.
    Owen D Jarman, Nitin Bohra, Peter Claus, Nicole Paczia, Tobias J Erb.
      Energy-conserving mechanisms are essential in supporting cellular life. Yet in synthetic biology, it remains a challenge to reconstruct such processes from the bottom-up and integrate them with other biological functions to create complex systems with life-like properties. Recent efforts to build higher-order cell-free metabolic networks have suffered from the fact that their central oxidation reactions are not coupled to energy conservation, causing kinetic and thermodynamic limitations. Here, we developed an artificial respiratory chain that we tailored to sustain rapid electron transfer in a CO2-fixing 16-enzyme catalytic cycle (crotonyl-CoA/ethylmalonyl-CoA/hydroxybutyryl-CoA), while also exploiting the concurrent electron flow for adenosine triphosphate synthesis. We demonstrate how such artificial respiratory chains can be further diversified to accept multiple electron entries and coupled to other biological functionalities, such as cell-free transcription-translation networks. Altogether, our work highlights the opportunities and challenges of directly integrating energy conservation mechanisms when building toward self-sustaining/self-energizing artificial life-like systems.
    Keywords:  artificial respiratory chains; energy conservation; energy modules; proteoliposomes; synthetic CO2 fixation
    DOI:  https://doi.org/10.1073/pnas.2613483123
  11. Exploration (Beijing). 2026 Jun;6(3): 20250303
    Bioinspired Regenerative Lignification Enables Ultra-Hard and Sustainable Bamboo Structural Materials.
    Jian Gan, Shaodi Zhang, Yuxiang Huang, Wenji Yu.
      The pursuit of sustainable structural materials requires combining high performance with renewable resources and low environmental impact. Here, we introduce a bioinspired regenerative lignification strategy that reconstructs lignin-like covalent networks directly within bamboo cell walls, condensing a multi-year natural hardening process into hours. Unlike conventional delignification-densification or polymer-filling approaches, this method preserves bamboo's hierarchical architecture while chemically stabilizing its matrix. The resulting ultra-hard bamboo exhibits a tensile strength of 503 MPa and a Brinell hardness of 42.1 HB, with weight-specific values surpassing steels and aluminum alloys. Multi-scale analyses reveal that the synergistic effects of cell-wall densification, enhanced cellulose crystallinity, and resin-cellulose cross-linking drive the performance breakthrough. Beyond strength and hardness, the material demonstrates remarkable flame retardancy, fungal resistance, and dimensional stability in water. Techno-economic and life-cycle assessments confirm competitive costs and substantially lower carbon footprints compared with conventional structural metals and plastics. This scalable, nature-inspired approach establishes a general pathway for transforming abundant biomass into next-generation sustainable materials with performance exceeding traditional engineering alloys.
    Keywords:  bamboo; biomimetic lignification; cell wall engineering; hardness
    DOI:  https://doi.org/10.1002/EXP.20250303
  12. Trends Biotechnol. 2026 Jul 03. pii: S0167-7799(26)00252-0. [Epub ahead of print]
    Bacterial spores as a modular platform for the production of amyloids for materials.
    Carina Dietz, Maren Kvilten, Simona Sebastiano, Cécile Formosa-Dague, Alexander Unger, Dieter Spiehl, Andreas Blaeser, Mikael Lindgren, Magnus Philipp, Johannes Kabisch.
      We present a proof-of-concept platform in which amyloids are displayed on the surface of engineered Bacillus subtilis spores for bioengineered materials. Amyloids possess high tensile strength, elasticity, and tunable assembly, but their use is limited by inaccessible native sources and low-yield or toxic heterologous expression. Spore-based display addresses these limitations by leveraging natural sporulation for controlled, surface-localized production without cross-membrane secretion, enabling simple purification by centrifugation. In this research article, spores were engineered to display native amyloid TasA and Humboldt squid suckerins 9 and 10 as fusions to the coat protein CotY. Western blotting and X-34 staining confirmed amyloid production and fibril formation, while semi-quantitative analysis determined binding sites. Atomic force microscopy revealed altered stiffness and surface ultrastructure, and incorporating these spores into resin-based 3D printing modified tensile strength. This modular, potentially scalable platform bypasses current production bottlenecks, leveraging established industrial infrastructure for future scale-up and rapid screening of synthetic amyloid-like proteins.
    Keywords:  3D printing; Bacillus subtilis; amyloid production; living biomaterial; spore surface display; squid ring teeth proteins
    DOI:  https://doi.org/10.1016/j.tibtech.2026.06.012
  13. mBio. 2026 Jul 02. e0119926
    Post-translational negative feedback loops are sufficient to coordinate synthesis of the gram-negative envelope during steady-state growth.
    Jaïrus Beije, Gregory Bokinsky.
      How gram-negative bacteria coordinate the synthesis of their multilayered envelopes is a long-standing fundamental question. We compile protein and metabolite measurements obtained from Escherichia coli to eliminate mechanisms that do not coordinate envelope synthesis during steady-state growth. These measurements reveal that envelope synthesis pathway expression and envelope precursor concentrations are both stable across growth rates, thus eliminating enzyme levels and metabolite levels as coordination mechanisms. We propose instead that envelope assembly pathways are coordinated by post-translational mechanisms that control a small number of enzymes and transport proteins, which in turn control upstream synthesis pathways via classic negative feedback. We further hypothesize that many signals that have been proposed to directly regulate envelope synthesis pathways act indirectly via known negative feedback loops.
    Keywords:  cell envelope; lipopolysaccharide; membrane biogenesis; metabolic regulation; phospholipids
    DOI:  https://doi.org/10.1128/mbio.01199-26
  14. Biointerphases. 2026 Jul 01. pii: 040801. [Epub ahead of print]21(4):
    Fiber-reinforced hydrogels: From multiscale structural design to advanced engineering applications.
    Bingtao Li, Anzhu Peng, Xinting Dong, Yujie Gao, Jindan Wu.
      Hydrogels are high-water-content polymer networks similar to those of soft tissues and have shown immense potential in fields such as tissue engineering, flexible electronics, and intelligent sensors. However, traditional hydrogels still face challenges such as low mechanical strength, poor toughness, and susceptibility to fatigue. Inspired by tough natural soft tissues (such as muscles and tendons), the introduction of a robust fibrous network into hydrogels enables effective stress transfer, crack bridging, and energy dissipation, thus overcoming the mechanical limitations of traditional hydrogels. This paper reviews fiber-reinforced hydrogels prepared from different reinforcing fibers (e.g., natural, synthetic, inorganic, and carbon-based), as well as the interfacial interactions between the fibers and the matrix (including physical entanglement, dynamic noncovalent bonds, and covalent bonds), and summarizes the preparation methods, such as in situ infiltration, directional freezing, and 3D printing. It also discusses their applications in the fields of medicine, sensing, and wearable devices and finally provides an outlook on current challenges such as precise interface regulation and large-scale intelligent manufacturing.
    DOI:  https://doi.org/10.1116/6.0005586
  15. Nat Chem Biol. 2026 Jul 03.
    Artificial metalloenzymes in complex biological environments.
    Guto G Rhys.
      Artificial metalloenzymes (ArMs) are proteins engineered to contain metal cofactors that often catalyze chemical reactions rarely or never observed in natural biological processes. They hold promise for applications including fine-chemical production, control of cellular function and therapeutics. Many of these applications are difficult to achieve due to cofactor inactivation in complex biological environments and cofactor-induced cellular stress. In this study, I explore the most recent strategies for developing robust, biocompatible ArMs that function in cell lysates, on cell surfaces or intracellularly. The pros and cons of developing and using ArMs in these three environments are described. I also examine how active ArMs might tolerate their environment, and the outstanding challenges and opportunities, including the need for simple methods of construction, improved catalytic performance and exploration of other reactions and microorganisms.
    DOI:  https://doi.org/10.1038/s41589-026-02249-3
  16. Nat Electron. 2025 Dec;8(12): 1272-1288
    A wireless subdural-contained brain-computer interface with 65,536 electrodes and 1,024 channels.
    Taesung Jung, Nanyu Zeng, Jason D Fabbri, Guy Eichler, Zhe Li, Erfan Zabeh, Anup Das, Konstantin Willeke, Katie E Wingel, Agrita Dubey, Rizwan Huq, Mohit Sharma, Yaoxing Hu, Girish Ramakrishnan, Kevin Tien, Paolo Mantovani, Abhinav Parihar, Heyu Yin, Denise Oswalt, Alexander Misdorp, Ilke Uguz, Tori Shinn, Gabrielle J Rodriguez, Cate Nealley, Tjitse van der Molen, Sophia Sanborn, Ian Gonzales, Michael Roukes, Jeffrey Knecht, Kenneth S Kosik, Daniel Yoshor, Peter Canoll, Eleonora Spinazzi, Luca P Carloni, Bijan Pesaran, Saumil Patel, Joshua Jacobs, Brett Youngerman, R James Cotton, Andreas Tolias, Kenneth L Shepard.
      Electrocorticography uses non-penetrating electrodes embedded in flexible substrates to record electrical activity from the surface of the brain. To use the technology to develop minimally invasive, high-bandwidth brain-computer interfaces, it will be necessary to improve the number of recording channels and the scalability of devices, which could be achieved by merging electrodes and electronics onto a single substrate. Here we report a 50-μm-thick, mechanically flexible micro-electrocorticography brain-computer interface that integrates a 256 × 256 array of electrodes, signal processing, data telemetry and wireless powering on a single complementary metal-oxide-semiconductor substrate. The device contains 65,536 recording electrodes, from which we can simultaneously record a selectable subset of up to 1,024 channels at a given time. Our chip is wirelessly powered, and when implanted below the dura, it can communicate bidirectionally with an external relay station outside the body. We show that the device can provide chronic, reliable recordings for up to two weeks in pigs and up to two months in behaving non-human primates from the somatosensory, motor and visual cortices, decoding brain signals at high spatiotemporal resolution.
    DOI:  https://doi.org/10.1038/s41928-025-01509-9
  17. Science. 2026 Jul 02. 393(6806): eadr3817
    Membrane protein solubilization and structure determination using de novo-designed proteins.
    Ljubica Mihaljević, David E Kim, Pooja D Bandawane, Helen E Eisenach, Andrew J Borst, Alexis Courbet, Connor Weidle, Kenneth D Carr, Everton Bettin, Qiushi Liu, Aldo T Trejos, Sagardip Majumder, Surabhi Kokane, Alexander Stevens, Edin Muratspahić, Thomas Schlichthaerle, Marc Expòsit, Xinting Li, Mila Lamb, Analisa Nicole Azcárraga Murray, Rashmi Ravichandran, Elizabeth C Williams, Shuyuan Hu, Lynda Stuart, Linda Grillová, Nicholas R Thomson, Michael Landreh, Pengxiang Chang, Lorenzo Giacani, Melissa J Caimano, Kelly L Hawley, Neil P King, David Baker.
      Developing therapies and vaccines against integral membrane proteins is hindered by their extensive hydrophobic surfaces, which complicate production and structural analysis. Here, we describe a general deep learning-based design approach for solubilizing native membrane proteins while preserving their sequence, fold, active-site, and ligand-binding properties. Genetically encoded de novo protein WRAPs [water-soluble RFdiffused amphipathic proteins] surround the lipid-interacting hydrophobic surfaces, rendering them thermostable and water-soluble without the need for detergents. We design WRAPs for both monomeric and oligomeric beta-barrel outer membrane proteins and helical multipass transmembrane proteins. A 2.95-angstrom-resolution cryo-electron microscopy structure of WRAPed mycobacterial porin demonstrates that WRAPs can be used for the structural determination of membrane proteins in solution. As a step toward syphilis vaccine development, we generated soluble versions of Treponema pallidum antigens.
    DOI:  https://doi.org/10.1126/science.adr3817
  18. bioRxiv. 2026 Jun 25. pii: 2026.06.23.733838. [Epub ahead of print]
    Agnostic material classification using differential de Bruijn graphs of DNA imprints.
    Rachael M Cox, Zoya T Ansari, Charlie D Johnson, Edward M Marcotte, Andrew D Ellington, Sanchita Bhadra.
      The wide variety of physical and chemical properties in materials makes the study of unknown substances challenging. We have previously proposed a theoretical framework for agnostic material characterization based on using nucleic acid 'imprints' of the materials and then analyzing material-specific patterns of derived sequences. Here we demonstrate an experimental and computational pipeline that can agnostically identify and distinguish varied materials based on DNA k -mer imprints and validate the ability of these imprints to distinguish closely related materials. This work lays the foundation for expansion of purely agnostic sensing technologies for the unbiased characterization and categorization of a much wider variety of biotic and abiotic materials.
    DOI:  https://doi.org/10.64898/2026.06.23.733838
  19. Polym Sci Technol. 2026 Jun 23. 2(6): 365-381
    Recyclable Photopolymers for Sustainable 3D Printing.
    Qirui Wu, Youyi Sun, Si Wu.
      The use of photopolymers for 3D printing facilitates high-precision fabrication of geometrically complex structures, offering exceptional dimensional accuracy and rapid curing capabilities that position it as a cornerstone of modern additive manufacturing. However, conventional photopolymers form permanently crosslinked networks, which are resistant to recycling. This inherent limitation generates persistent waste streams that are fundamentally incompatible with circular economy principles. Consequently, the development of recyclable photopolymers that maintain printability while enabling closed-loop material recovery represents a critical Frontier for sustainable manufacturing. Advancing these materials will remain essential for reconciling technological progress with environmental stewardship in the foreseeable future. This review examines recent breakthroughs in recyclable photopolymer systems for 3D printing. First, mainstream photopolymerization techniques compatible with recyclable materials are outlined, followed by an elucidation of core design strategies incorporating chemical depolymerization, thermo-mechanical reprocessing, and noncovalent interactions. Fundamental recycling mechanisms are detailed alongside performance modulation methodologies. Furthermore, emerging applications in soft robotics, wearable devices, and bioelectronic devices where recyclable photopolymers enable multifunctional devices are highlighted. Finally, persistent challenges regarding network durability and recycling efficiency are addressed, and future research directions toward truly sustainable 3D printing are proposed.
    Keywords:  3D printing; depolymerization; noncovalent bond; recyclability; reprocessing
    DOI:  https://doi.org/10.1021/polymscitech.5c00144
  20. Biomacromolecules. 2026 Jun 30.
    Navigating the Forest of Lignin-Derived Monomers for Polymer Synthesis.
    Peter Olsén, Elena Subbotina.
      The field of lignin-based polymeric materials is undergoing rapid development, driven by increasing sustainability demands. However, progress in lignin-derived materials is often pursued from different disciplinary perspectives─biomass chemistry, organic synthesis, and polymer materials science─using field-specific metrics, resulting in fragmented knowledge. This Perspective examines the lignin-to-materials pathway by connecting advances in the conversion of lignin into platform molecules, their transformation into monomers, and the synthesis of polymeric materials through representative examples. We perform rough estimates of sustainably available lignin streams and compare them with current polymer production, indicating that lignin could potentially supply aromatic monomers at scales comparable to existing markets. Through analysis of key literature on lignin-to-monomers and monomers-to-polymer strategies, we identify critical directions for lignin-to-materials development. These include refinery concepts that utilize complex lignin-derived substrates as primary building blocks, prioritizing the use of their inherent functionality before stepwise defunctionalization, and adopting application-driven materials design, in which the requirements of a target application guide monomer and polymer selection rather than attempting to reproduce the molecular structures of the petroleum-derived polymers currently used for those applications.
    DOI:  https://doi.org/10.1021/acs.biomac.6c00494
  21. Nat Mater. 2026 Jul;25(7): 1069
    High-precision memristor-based computing.
      
    DOI:  https://doi.org/10.1038/s41563-026-02672-w
  22. ACS Nano. 2026 Jun 30.
    Chemically Fueled Interfacial Supramolecular Polymerization.
    Zhiqin Xia, Preetika Rastogi, Xuefei Wu, Zachary Fink, Paul D Ashby, Brett A Helms, Thomas P Russell.
      Systems capable of dissipative self-assembly emulate the dynamic, adaptive behavior of biological systems, yet spatial control over this behavior remains a challenge. Here, we show how to generate chemically fueled supramolecular polymers at liquid-liquid interfaces by coupling a chemical reaction network with an orthogonal self-assembly based on host-guest interactions and metal-ligand coordination. Confinement to the interface yields readily tunable lifetimes for the polymers as well as an ability to undergo controlled depolymerization in response to stimuli, including redox cues or competitive guests. These polymers can jam at the interface enabling the generation of all-liquid constructs that are time-programmable and multistimuli responsive, providing a versatile platform for designing adaptive, out-of-equilibrium soft materials.
    Keywords:  chemical fuels; dissipative assembly; oil−water interface; stimuli responsiveness; structured liquids; supramolecular polymers
    DOI:  https://doi.org/10.1021/acsnano.6c06152
  23. Biofabrication. 2026 Jun 30. 18(3):
    Floatony formation in liquid environments: liquid drawing-based fabrication of three-dimensional microbial structures.
    Hidetaka Taniguchi, Mai Miyauchi, Ippei Inoue, Masayoshi Tanaka.
      The spatial organization of microorganisms plays a pivotal role in regulating microbial physiology, community behavior, and ecological interactions. However, reconstructing such three-dimensional (3D) microbial architecturesin vitroremains a major challenge because conventional culture systems rely on solid or gel-based matrices that restrict microbial motility and molecular diffusion. Here, we introduce 'floatony', a liquid-based strategy for the fabrication of spatially defined microbial colonies using liquid drawing technology. This approach enables the formation and retention of 3D microbial assemblies entirely within a liquid environment, without solidification or crosslinking. UsingE. colias a model organism, we examined how the rheological properties of the supporting liquid matrix influenced the stability of drawn structures of microbial assemblies. Although the optimal conditions depend on the molecular architecture of thickening agents, we identified an empirical design criterion-tanδ< 1.8-under which 3D structures of microbial assemblies were stably retained while maintaining low viscosity (∼10-1Pa·s) conducive to efficient molecular diffusion. Enzymatic activity assays confirmed thatE. colimaintained functional enzyme activity within the supporting liquid matrix, and that the diffusion of low-molecular-weight reaction products was preserved. Furthermore, complex two-dimensional and 3D structures of microbial assemblies were successfully fabricated and visualized in a liquid, including floating 3D structures, as confirmed by fluorescence imaging. This liquid drawing-based approach provides a new experimental framework for reconstructing and studying spatially organized microbial systems, offering opportunities for investigating microbial interactions and developing engineered living materials beyond conventional solid-supported platforms.
    Keywords:  floatony; liquid drawing; rheology; three-dimensional microbial organization
    DOI:  https://doi.org/10.1088/1758-5090/ae7ed4
  24. Nat Biotechnol. 2026 Jul 02.
    Unlocking the chemical potential of filamentous fungi using prime editing.
      
    DOI:  https://doi.org/10.1038/s41587-026-03219-9
  25. Cell Syst. 2026 Jul 01. pii: S2405-4712(26)00138-9. [Epub ahead of print] 101656
    High-throughput DNA engineering by mating bacteria.
    Takeshi Matsui, Po-Hsiang Hung, Han Mei, Xianan Liu, Fangfei Li, John Collins, Weiyi Li, Darach Miller, Neil Wilson, Esteban Toro, Geoffrey J Taghon, Gavin Sherlock, Sasha Levy.
      We introduce SCRIVENER (sequential conjugation and recombination for in vivo elongation of nucleotides with low errors), an in vivo DNA assembly platform that streamlines and scales DNA engineering. SCRIVENER combines bacterial conjugation, in vivo DNA cutting, and homologous recombination to stitch DNA blocks together by mating E. coli in large arrays or pools. This approach is simpler, cheaper, and higher throughput than methods requiring DNA to be moved in and out of cells. We performed over 5,000 assemblies with 2 to 19 blocks (240 bp-12 kb) and assembled constructs up to 81 kb with high fidelity. Most errors are deletions between long repeats, but SCRIVENER minimizes their impact by enabling high-replication assembly and sequence verification at a nominal additional cost per replicate. The platform enables combinatorial library construction and DNA block reuse without PCR and is therefore a powerful tool to accelerate DNA design-build-test-learn cycles. A record of this paper's transparent peer review process is included in the supplemental information.
    Keywords:  DNA assembly; DNA engineering; DNA reuse; DNA synthesis; composability; conjugation; genetic tools; high-throughput; in vivo; plasmid engineering
    DOI:  https://doi.org/10.1016/j.cels.2026.101656
  26. J Am Chem Soc. 2026 Jul 01.
    Solvent-Driven Biphasic Architectures in Polymer Gels via Polymerization-Induced Solvent Phase Separation.
    Yuji Kamiyama, Ryota Tamate.
      Polymer gels with biphasic architectures enable diverse functions, such as enhanced mechanical robustness and programmable drug release. Conventional fabrication of biphasic gels typically relies on the copolymerization of monomers with differing solvent affinities, which constrains structural diversity and tunability. In this study, we introduce "polymerization-induced solvent phase separation" (PI-SPS) as a novel and facile solvent-driven strategy for constructing biphasic gels. Polymerization of a homogeneous precursor solution containing two mutually immiscible solvents and a monomer triggers solvent demixing, yielding a hierarchical structure in which a polymer-rich continuous phase composed of the good solvent encapsulates dispersed droplets of the less favorable solvent-rich phase. We demonstrate the generality of PI-SPS across systems comprising water, organic solvents, and ionic liquids. The resulting biphasic architectures confer emergent properties, including self-healing ability, shape-memory behavior, and enhanced crack resistance, with a fracture energy of 4600 J m-2 derived from the spatial organization of solvent domains and polymer networks. Overall, the PI-SPS strategy provides a versatile platform for engineering multiphase soft materials through controlled tuning of solvent affinities.
    DOI:  https://doi.org/10.1021/jacs.6c03722
  27. Adv Healthc Mater. 2026 Jun 29. e05938
    Spontaneous Helical Alignment of Smooth Muscle Cells to Form a Medial Layer for Engineered Microvasculature.
    Victoria D Vest, Katherine J Young, Isabella K Holtz, Mark Mc Veigh, James D West, Leon M Bellan.
      Microscale small resistance vessels (SRVs) are key regulators of local vascular resistance and tissue perfusion, yet, compared to efforts toward engineering capillaries ("exchange vessels") and vascular grafts ("conduit vessels"), there has been limited effort devoted to engineering SRVs with appropriate architecture and function. Natural SRVs rely on a medial layer of helically arranged contractile smooth muscle cells (SMCs) to modulate lumen diameter, thereby regulating local fluidic resistance. However, current SRV-scale engineered vasculature either lacks an SMC layer or contains unaligned or non-contractile SMCs, rendering such constructs incapable of recapitulating the essential function of natural SRVs. Here, we demonstrate that appropriate choice of fabrication parameters can promote spontaneous helical alignment of SMCs seeded on the walls of SRV-sized channels within a hydrogel (without any patterning of topography or binding sites). The resulting alignment angle is sensitive to the composition of extracellular matrix proteins coating the attachment surface, SMC seeding density, and channel diameter. SMCs within these constructs exhibit functional and morphological hallmarks of a contractile phenotype, including biochemical response to vasoconstrictor endothelin-1 (ET-1). Establishing an aligned, contractile phenotype SMC layer represents a critical step toward engineering SRVs with vasoreactive functionality mimicking that of natural vessels.
    Keywords:  engineered microvasculature; resistance vessels; tissue engineering
    DOI:  https://doi.org/10.1002/adhm.202505938
  28. Nat Commun. 2026 Jul 02. pii: 5788. [Epub ahead of print]17(1):
    Dissecting autonomous enzymatic variability in single cells.
    Christian Gnann, Alina Sigaeva, Trang Le, Anthony J Cesnik, Sanem Sariyar, Diana Mahdessian, Rutger Schutten, Preethi Raghavan, Manuel D Leonetti, Cecilia Lindskog, Mathias Uhlén, Ulrika Axelsson, Emma Lundberg.
      Metabolic enzymes perform life-sustaining functions in various cellular compartments. Anecdotally, metabolic activity is observed to vary between genetically identical cells, which impacts drug resistance, differentiation, and immune cell activation. However, no large-scale resource systematically reporting metabolic cellular heterogeneity exists. Here, we leverage imaging-based single-cell spatial proteomics to reveal the extent of non-genetic variability of the human enzymatic proteome, as a proxy for metabolic states. Nearly two fifths of enzymes exhibit cell-to-cell variable expression, and half localize to multiple cellular compartments. Metabolic heterogeneity arises largely autonomously of cell cycling, and individual cells reestablish these myriad metabolic phenotypes over several cell divisions. We reveal through multiplexed imaging that metabolic states are continuous and that the correlation between metabolic pathways is metabolic state dependent. These results establish cell-to-cell enzymatic heterogeneity as an organizing principle of cell biology that may rewire our understanding of drug resistance, treatment design, and other aspects of medicine.
    DOI:  https://doi.org/10.1038/s41467-026-74172-z
  29. Science. 2026 Jul 02. 393(6806): 12-13
    Lab creates new kind of synthetic cell.
    Kai Kupferschmidt.
      "SpudCells" can grow and divide but still have major limitations.
    DOI:  https://doi.org/10.1126/science.aek1826
  30. Sci Adv. 2026 Jul 03. 12(27): eaee1510
    Large-area, photo-programmable 2D semiconductors with chromic molecular functionalization.
    Jaehoon Ji, Yin Liang, Jinpeng Tian, Jingtao Tan, Jaerin Kim, Satya Butler, Haining Mao, Gloria Liu, Saien Xie.
      Reconfigurable electronics expands device functionality and promises previously unknown computing paradigms, as the channel layer characteristics can be dynamically controlled. Two-dimensional semiconductors coupled with photo-responsive chromic molecules offer a compelling route as atomically thin channels are highly sensitive to molecular conformation changes. However, most demonstrations have been limited to microscale single-flake devices, limiting scalability and technological relevance. Here, we report an optically reconfigurable platform integrating centimeter-scale monolayer WS2 and WSe2 with an azobenzene (Azo) overlayer. Wavelength-selective trans-cis Azo photoisomerization generates a reversible interfacial dipole that serves as an optical gate, enabling precise and uniform modulation of both electron and hole densities (~2.5 × 1012 cm-2) over large areas. This optical actuation further supports spatially programmable patterning of optoelectronic properties and delivers repeatable modulation across large transistor arrays. Together, these results establish a scalable smart materials platform for reconfigurable optoelectronics that is light-programmable.
    DOI:  https://doi.org/10.1126/sciadv.aee1510
  31. PLoS Comput Biol. 2026 Jun 29. 22(6): e1014469
    Systematic design of auxotrophic strains and media conditions to probe metabolic functions in E. coli.
    Roghaye Mohammadbeygi, Patrick F Suthers, Fang-Yu Chung, Brian F Pfleger, Costas D Maranas.
      Despite progress in automated gene annotation, many deficiencies and knowledge gaps remain, even for well-studied organisms. Of particular concern is the accuracy and detail of annotations for transporters of various organic substrates and products of metabolism and for enzymes that do not share sequence homology with well-characterized strains. Unfortunately, annotation errors present in earlier genome-scale metabolic (GSM) models propagate to newer models with few opportunities for later correction. Here, we introduce a systematic computational procedure that applies the Escherichia coli genome-scale metabolic model iML1515, extended with transcriptional regulatory rules, to design auxotrophs that can grow on glucose but fail to grow on different carbon substrate(s) unless rescued with the addition of an ORF encoding a complementation metabolic function (transport and enzymatic reactions). Using the E. coli GSM model supplemented with regulatory rules that quantify growth/no growth outcomes on different organic substrates, we identified 258 distinct auxotrophic designs (97 single-gene, 142 double-gene, and 19 triple-gene knockouts) for which specific single functions can uniquely complement them. Experimental validation of 61 single-knockout strains demonstrated 59% confirmed auxotrophy and 28% partial auxotrophy. We envision that this collection of auxotrophic strains can be used to disambiguate the metabolic role of unannotated or poorly annotated genes.
    DOI:  https://doi.org/10.1371/journal.pcbi.1014469
  32. Small. 2026 Jul 03. e74386
    3D-Printed Milli-Fluidic Mixing-Extrusion Platform for Continuous, High-Throughput LNP Production.
    Leekang Jeon, Seeun Kim, Hanjin Seo, Hyun Su Lee, Gi-Su Na, Gi-Ra Yi, Hyomin Lee.
      Lipid nanoparticles (LNPs) have emerged as a prominent delivery vehicle for therapeutics such as mRNA vaccines and genetic medicines. However, current manufacturing technologies struggle to balance precision, scalability, and cost-effectiveness. While microfluidic mixing offers excellent particle control, it often faces operational challenges, including channel fouling and a reliance on costly single-use chips that create bottlenecks for reproducible and scalable production of LNPs. Conversely, bulk methods lack uniformity, and conventional extrusion remains a labor-intensive batch process. Here, we report a hybrid continuous synthesis platform that integrates a reusable 3D-printed milli-fluidic mixer with inline membrane extrusion. By engineering a robust 3D internal architecture at the milli-scale, this system achieves rapid mixing while mitigating clogging risks associated with micro-channels. Our platform also offers a durable, easy-to-clean alternative that enhances process reproducibility while the integrated design enables single-pass refinement of LNPs, streamlining the production workflow to achieve high-quality, uniform LNPs at flow rates of up to 20 mL min-1. Overall, our study provides a scalable, cost-effective, and contamination-resistant pathway for industrial LNP manufacturing, overcoming the limitations of existing disposable cartridge-based systems.
    Keywords:  3D‐printing; extrusion; high‐throughput; lipid nanoparticles; mixing
    DOI:  https://doi.org/10.1002/smll.74386
  33. Cell Syst. 2026 Jul 01. pii: S2405-4712(26)00134-1. [Epub ahead of print] 101652
    A data-driven modeling framework for mapping genotypes to synthetic microbial community functions.
    Yili Qian, Sarvesh D Menon, Hanchen Huang, Nick Quinn-Bohmann, Sean M Gibbons, Ophelia S Venturelli.
      Synthetic microbial communities offer valuable insights into the mechanisms that govern community functions, and they can be designed to achieve desired functions in order to address societal challenges in precision medicine and agriculture. Existing computational models for predicting synthetic community functions use species abundances as inputs; this makes it impossible to predict the effects of species not included in training data. We bridge this gap using a data-driven community genotype-function (dCGF) modeling framework. By lifting the representation of each species to a high-dimensional genetic feature (GF) space, dCGF learns a mapping from community GF matrices to community functions. Using in silico and experimental data, we demonstrate that dCGF can accurately predict community functions that are composed partly or entirely of new species. In addition, dCGF can generate hypotheses about the contribution of specific GFs to community functions. In sum, dCGF uses genetic information to model synthetic microbial communities in order to empower their model-driven design. A record of this paper's transparent peer review process is included in the supplemental information.
    Keywords:  community function; genetic information; machine learning; synthetic microbial communities; systems biology
    DOI:  https://doi.org/10.1016/j.cels.2026.101652
  34. Biomater Sci. 2026 Jul 01.
    Bioorthogonally reinforced injectable granular hydrogels synergizing ECM mimicry with microporosity for skin tissue engineering.
    Akshat Joshi, Yasuhiro Ikegami, Yingnan Yue, Yongdeok Jo, Akhilesh Agrawal, Meenakshi Kamaraj, Kawailani Lilly, Jooyoung Park, Diego N Rodriguez-Sanchez, Ujjayan Majumdar, Aayush Gupta, Ji-Hoo Lee, Suk-Jung Oh, Shinichi Aishima, Hiroyuki Ijima.
      Designing injectable biomaterials that simultaneously recapitulate extracellular matrix (ECM) composition while maintaining interconnected microporosity remains a central challenge in regenerative scaffolds. Granular hydrogels offer unique opportunities to address this limitation because their jammed microgel architecture inherently supports injectability and cell-accessible porosity. Here, we report a bioorthogonally reinforced ECM-mimetic granular hydrogel platform assembled from complementary gelatin and hyaluronic acid-derived microparticles that anneal through dynamic hydrazone coupling. By integrating collagen-mimetic adhesive domains with glycosaminoglycan-mimetic hydrated phases within a jammed microgel network, the system recreates key biochemical and structural features of native ECM. The resulting hydrogels exhibit rapid self-assembly, pronounced shear-thinning injectability, and stable interparticle reinforcement while preserving interconnected microporosity. Consequently, the material functions both as an injectable scaffold and as a support-free bioink for extrusion-based 3D printing. The microporous architecture supports progressive cellular infiltration and spreading in vitro, while in vivo evaluation in a splinted full-thickness wound model demonstrates accelerated wound closure, enhanced granulation tissue formation, and increased neovascularization compared with bulk hydrogel controls. These findings establish ECM-mimetic granular hydrogels as a versatile platform for injectable and printable biomaterials in skin tissue regeneration.
    DOI:  https://doi.org/10.1039/d6bm00379f
  35. Sci Adv. 2026 Jul 03. 12(27): eaec4197
    Toward autonomous robotic-assisted and microrobotic surgery.
    Sungyun Yang, Byung Ha Kang, Hyeongho Min, Juan P Wachs, Farshid Alambeigi, Jaydev P Desai, Pierre E Dupont, Kurt Yaeger, Katherine Anderson, Alan Kuntz, Ron Alterovitz, Robert J Webster, Nobuhiko Hata, Janani S Reisenauer, McKenna Clinch, Alex Abramson, Jie Ying Wu, Tommaso Ranzani, Peter C Kim, Alex S Huang, Cheng Sun, Hao F Zhang, Cameron N Riviere, Eric R Henderson, Michael Yip, Xiaoguang Dong, Daniel A Wollin, David H Gracias, Lamar O Mair, Michael Karpelson, Robert J Wood, Itai Cohen, Michael S Strano.
      Autonomous robotic-assisted surgery (RAS) has emerged as a promising objective in biomedical technology, further enhanced by miniaturization toward microrobotic-assisted surgery (μ-RAS). This reduction in scale promises minimally invasive, partially or fully automated surgical procedures, with the potential to reduce patient recovery times, lower medical costs, and enable previously unavailable procedural options. This perspective highlights the specific advances in RAS that potentially map to the microscale (μ-RAS), organized across five surgical domains: endovascular, endoluminal, laparoscopic, ophthalmic, and orthopedic. We examine both clinical demands and technological advances in surgical robotics and identify the key innovations required for progress across these surgical fields. Our contribution is distinct in combining the perspectives of both surgical experts and bioengineering innovators, outlining a roadmap for the advancement and eventual integration of autonomous RAS and μ-RAS into mainstream surgical practice.
    DOI:  https://doi.org/10.1126/sciadv.aec4197
  36. Langmuir. 2026 Jul 01.
    Spontaneous Phase Separation Enables Rapid, Polymerization-Free Fabrication of Gels.
    Namrata Priyadarshinee, Vidhi Saxena, Aniruddha Kambekar, Gaurav Chauhan, Karthik Pushpavanam.
      Hydrogels are cross-linked polymeric networks with wide applications in drug delivery, tissue engineering, biosensing, and environmental remediation. These hydrogels additionally host living cells, small molecules, and biological propagules, which further expand the applications of these materials. However, most, if not all, fabrication methods require covalent modifications. In this work, by deliberately selecting polymers with a known propensity to phase separate and formulating compositions far from the binodal boundary, we demonstrate the propensity of the system to transition directly into viscoelastic liquids or gels. This behavior is demonstrated using a model system of poly(ethylene glycol) (PEG) and dextran (DEX). We carried out rheological studies to provide insights into the viscoelastic behavior of these gels. We systematically characterized the gels through colorimetric assays, FTIR, MALDI-TOF, and thermogravimetric analysis (TGA) to discern the molecular compositions and solvent content of the gels. These experimental findings are supplemented with coarse-grained (CG) simulation insights to investigate the mechanistic origins of phase separation propensity with varying molecular weights of DEX. We utilized coexisting densities in the two phases using CG simulations to predict the role of DEX molecular weight in the partitioning of PEG and DEX in the two phases. Finally, we exploit the fabricated gel's ability to encapsulate live cells, antibiotics, and plant seeds. We anticipate that this ATPS-based fabrication technique will provide a scalable, cross-linker-free route to multifunctional gels, enabling advanced applications in drug delivery and responsive materials.
    DOI:  https://doi.org/10.1021/acs.langmuir.6c01903
  37. Adv Mater. 2026 Jul 01. e73847
    Engineering Layered Magnetic Hydrogels for Cell Placement via Shear and Magnetic Field-Induced Assembly.
    Guillermo Camacho, Jose R Morillas, Jesús García-Gutiérrez, Stefania Nardecchia, Óscar Martínez-Cano, Juan de Vicente.
      The design of hydrogel-based artificial tissues capable of reversible, programmed, and complex motions requires both stimuli-responsiveness and structural anisotropy. In this work, non-unidirectional anisotropies are generated in biocompatible hydrogels by structuring magnetic particle suspensions into lamellar architectures through two distinct routes: the application of an unsteady magnetic field to a quiescent sample, and the superposition of a steady magnetic field with shear flow. In both approaches, magnetic particles undergo directed self-assembly within a polymer matrix that subsequently gels, thereby preserving the formed structures. We analyze the assembly kinetics, characterize the resulting lamellar patterns, and construct phase diagrams for each method. The morphology and periodicity of the lamellae are shown to depend strongly on geometric confinement, enabling tunable interlamellar spacing from tens to hundreds of microns. Crucially, it is demonstrated that the resulting layered hydrogels can confine human fibroblasts between adjacent particle-rich lamellae, maintain cell viability above 95% over 7 days of culture, and promote preferential cell alignment parallel to the layered structures. These findings establish magnetic field-directed lamellar structuring as a versatile route to anisotropic hydrogels with programmable internal architecture, opening new opportunities in tissue engineering, bioactuation, and soft robotics.
    Keywords:  anisotropic hydrogel; biomaterial; bioprinting; lamella; layer; magnetic hydrogel; magnetorheological fluid; pattern; tissue engineering
    DOI:  https://doi.org/10.1002/adma.73847
  38. Nat Commun. 2026 06 29. pii: 5623. [Epub ahead of print]17(1):
    Cellular replisomes are powered by flex-fuel motors for unwinding DNA.
    Fahad Rashid, Sushil Pangeni, Chuan Liu, Harish Kumar, Gyeongtae Sun Moon, Qianyun Yan, Taekjip Ha, James M Berger.
      DNA replication relies on hexameric, ring-shaped helicases to unwind parental DNA for supporting fork progression over tens of thousands of base pairs. Oddly, biochemical studies have suggested that, on their own, replicative helicases are rather limited motors that struggle to couple rapid movement to nucleotide turnover (typically believed to be solely ATP). Here, single-molecule studies reveal that when properly loaded, the Escherichia coli (E. coli) replicative helicase, DnaB, is a tremendously fast single-stranded DNA translocase that moves up to three times more rapidly than the replisome (3 knt/s). Translocation is highly processive, resistant to pulling force/high salt, and can displace short, 3'-tailed DNA duplexes without apparent changes in speed. Surprisingly, we find that the loader for DnaB, DnaC, can use any rNTP or dATP for depositing DnaB onto ssDNA and that the helicase itself also must hydrolyze nucleotide for stable loading. DnaB translocation also turns out to be supported by any r/dNTP, a property shown to extend to the eukaryotic CMG replicative helicase. Overall, the DNA unwinding engines that support cellular replisomes are highly indiscriminate of their fuel source, a feature that may be of utility during times when cells encounter nucleotide pool stress but have committed to DNA synthesis.
    DOI:  https://doi.org/10.1038/s41467-026-73652-6
  39. Nat Protoc. 2026 Jun 30.
    High-throughput measurements of protein domain functions using magnetic separation.
    Abby R Thurm, Josh Tycko, Connor H Ludwig, Mark Ragheb, Nicole DelRosso, Gaelen T Hess, Michael C Bassik, Lacramioara Bintu.
      High-throughput screening of protein domains enables the systematic discovery of protein sequences that encode specific cellular functions. Fluorescence-activated cell sorting-based assays have long been the standard readout for such screens but remain time- and resource-intensive, imposing practical limits on library size and coverage. Here we describe a scalable magnetic separation-based workflow that provides an alternative to fluorescence-activated cell sorting for screening large protein libraries in mammalian cells. We engineered a modular synthetic surface marker, consisting of a fusion between the fragment crystallizable (Fc) region of human immunoglobulin G and the transmembrane domain of platelet-derived growth factor receptor-β, that allows cells to be magnetically separated on the basis of surface reporter expression using Protein G-coated magnetic beads. The procedure covers pooled library cloning, lentiviral delivery, magnetic separation and sequencing-based quantification, enabling reproducible screening of more than 100,000 protein domain variants. The approach is suitable for the identification of functional protein domains capable of transcriptional and post-transcriptional RNA regulation and may lead to the selection of improved transmembrane domains for efficient protein surface display. The entire workflow, from library design to data analysis, can be completed in 4-6 weeks and requires skills in cell culture, molecular cloning and computational techniques. This scalable and accessible Protocol enables researchers to systematically measure protein domain functions across biological contexts, thus accelerating both biological discovery and protein engineering.
    DOI:  https://doi.org/10.1038/s41596-026-01397-z
  40. Biofabrication. 2026 Jul 02.
    Inorganic biomaterials-reinforced printable hydrogel modulating regenerative microenvironments for tissue repair.
    Ziyi Zhao, Chengtie Wu.
      Complex tissue/organ regeneration is a well-orchestrated biological process that orchestrated by coordinate effort of neural, vascular and immune systems, accompanied with multiple cellular interaction and signals crosstalk. The beneficial pro-regenerative microenvironments are of great significance for regulating tissue-resident cell viability, migration and differentiation to direct tissue repair process. 3D bioprinting is an advanced biomanufacturing strategy that utilizes hydrogelcontaining bioinks to fabricate cell-laden scaffolds, but they face the limitations of insufficient bioactivity. Inorganic biomaterials have been recognized as effective bioactive agents owing to their tunable chemical composition, topographical architectures, and physiochemical properties, which can overcome the limitation of printable hydrogel and broaden their potential biological applications. This review primarily concentrates on the design of inorganic biomaterials-reinforced printable hydrogel for modulating regenerative microenvironments including neural, vascular, and immune regulation, and summarizes the recent progress of their applications for tissue and organ regeneration. It begins with an introduction of inorganic biomaterials augmenting the biophysical and the biochemical properties of 3D-printed hydrogel, especially highlighting the improvement of topographical cues, mechanical strength, external field responsiveness, and releasing bioactive components for regulating various tissue microenvironments. Subsequently, recent advancements of inorganic biomaterialsreinforced printable hydrogel in regenerating various tissues including musculoskeletal system, skin, and cardiac tissues are systematically reviewed. Finally, current challenges and future perspectives in the development of inorganic biomaterials-reinforced printable hydrogel are proposed. This review may offer a universal strategy for the design of novel bioinks in combination with inorganic biomaterials and printable hydrogel, which shows great potential for engineered biofabrication and complex tissue/organ regeneration.
    Keywords:  3D bioprinting; bioinks; inorganic biomaterials; regenerative microenvironments; tissue repair
    DOI:  https://doi.org/10.1088/1758-5090/ae8580
  41. Cell Syst. 2026 Jul 01. pii: S2405-4712(26)00136-5. [Epub ahead of print] 101654
    Living bacterial reservoir computers for information processing and sensing.
    Paul Ahavi, Thi-Ngoc-An Hoang, Philippe Meyer, Sylvie Berthier, Federica Fiorini, Florence Castelli, Olivier Epaulard, Audrey Le Gouellec, Jean-Loup Faulon.
      We introduce a systems-level approach to sensing and computing in which Escherichia coli acts as a living reservoir computer, performing complex information processing through its native growth responses without requiring genetic modification or specialized instrumentation. We validate this framework by accurately classifying early-stage COVID-19 plasma samples according to subsequent disease severity using only bacterial growth data, highlighting its prognostic potential without the need for infrastructure-dependent methods. By controlling nutrient media compositions, we also demonstrate that E. coli growth encodes nonlinear transformations that outperform linear regression, support vector machines, and multilayer perceptrons across diverse regression and classification tasks. More broadly, simulations across genome-scale metabolic models from multiple bacterial species support a link between phenotypic diversity and computational capacity. These findings position biological reservoir computing as a robust, scalable, and low-cost platform for intelligent biosensing, diagnostics, and hybrid bio-digital computation, while providing new mechanistic insights into the computational capabilities of living systems.
    Keywords:  bacterial computing; biosensing; cellular computing; disease prognosis; machine learning; medical diagnostics; microbial growth dynamics; physical reservoir computing; reservoir computing
    DOI:  https://doi.org/10.1016/j.cels.2026.101654
  42. ACS Synth Biol. 2026 Jul 01.
    Engineering Modular Cargo Loading Strategies for Carboxysome-Derived Protein Particles.
    Claudia A Mak, Rachelle M Baumann, Anthony G Vecchiarelli.
      Bacterial microcompartments (BMCs) are a diverse and widespread class of self-assembling protein-based organelles consisting of a semipermeable protein shell encapsulating an enzymatic core. Isolated BMC shell proteins have been shown to assemble into alternative superstructures such as flat sheets and nanotubes. The self-assembly and modularity of BMC shell proteins make them of great interest as modular platforms for applications involving scaffolding, immobilization, and compartmentalization. While the assembly of BMC shell proteins into higher-order structures has been well-studied, the design of controllable and modular cargo loading is underdeveloped in comparison. Recently, we reported the pH-controlled assembly of CcmK2, the major hexameric shell protein of the β-carboxysome BMC, into monodisperse mesh-like microscale particles. Here, we develop a suite of encapsulation strategies for stochastic or targeted loading of various cargos, as well as the direct conjugation of cargo to CcmK2 particles. Our systematic analysis demonstrates that cargo loading and particle assembly can be modulated by the choice of recruitment strategy and the order of cargo introduction. Our findings also reveal a cooperative cargo loading mechanism during assembly that influences particle sizing and apparent morphology. Our study serves as a blueprint for the rational design of tunable cargo loading into engineered BMC-derived microcompartment systems for diverse biotechnological applications.
    Keywords:  bacterial microcompartment; biomaterial; carboxysome; cargo loading; protein particle; self-assembly
    DOI:  https://doi.org/10.1021/acssynbio.6c00354
  43. ACS Appl Mater Interfaces. 2026 Jun 29.
    Dual-Modulus Microcone Array for Graded Tactile Sensing and Intelligent Slip Detection.
    Zhen Wei, Chunjiang Zhao, Yuehua Huang, Xinglan Fu, Wei Liu, Yi Xiong, Guanglin Li.
      This work reports a dual-modulus microcone array for graded tactile sensing and intelligent slip detection. The asymmetric microstructure─comprising hollow and solid polydimethylsiloxane/carbon nanotube (PDMS/CNT) microneedle arrays with distinct Young's moduli (460.8 kPa vs 581.2 kPa)─produces a hierarchical mechanical response fundamentally different from conventional single-modulus designs. This structural design yields high sensitivity (9.55 kPa-1) over a broad pressure range (0.1-450 kPa), fast response/recovery (68/51 ms), and durability exceeding 10000 cycles. The superhydrophobic surface (contact angle 156.5 ± 1.0°, sliding angle <2°) ensures stable operation in wet and variable-temperature environments (10-70 °C). Integrated with a one-dimensional convolutional neural network for slip detection and adaptive feedback control, the sensor enables real-time grip force regulation during delicate object manipulation, minimizing mechanical damage and contamination. This work establishes a materials platform that couples interfacial engineering with machine learning-enhanced perception, with implications for soft robotics, wearable electronics, and intelligent human-machine interfaces.
    Keywords:  dual-modulus microstructure; graded deformation; slip detection; superhydrophobicity; tactile sensor
    DOI:  https://doi.org/10.1021/acsami.6c08642
  44. bioRxiv. 2026 Jun 23. pii: 2026.06.21.729417. [Epub ahead of print]
    Programming T cells for intercellular genome editing.
    Kevin M Wasko, Madeleine Maker, Wayne Ngo, Kai Chen, Enbo Ma, Rithu Pattali, Enzo Chen, Trevor Leung, Jonathan Braverman, Jennifer A Doudna.
      Therapeutic genome editing requires delivery of editing molecules to defined cell types, but targeting specificity and efficiency are currently limited. We hypothesized that properties inherent to immune cells, including tissue infiltration and programmed cell recognition, could be harnessed to engineer a cell-based delivery system. We show here that T cells can both produce and transfer editing machinery to target cells. In response to a programmable ligand, engineered T-lymphoid cells can transfer enzymes using complex spatiotemporal logic and deliver cargo in a cell contact-dependent or -independent manner. We demonstrate feasibility of this approach in primary human T cells, establishing a customizable genetic circuit for macromolecular delivery controlled by intercellular interactions.
    DOI:  https://doi.org/10.64898/2026.06.21.729417
  45. Biotechnol Adv. 2026 Jul 02. pii: S0734-9750(26)00169-2. [Epub ahead of print] 108963
    Advancing synthetic biology with engineered chemically inducible gene regulatory systems.
    Xinyue Li, Youzhi Su, Yangzi Zhang, Yuan Su, Chao Ji, Wenjie Zheng, Ru Meng, Wenbiao Shi, Longjiao Zhu, Wentao Xu.
      Chemically inducible gene regulatory systems, with inducible promoters as their core regulatory elements, are central to advancing synthetic biology by enabling precise, dynamic, and orthogonal control of gene expression in response to chemical signals. Recent advances have moved the field from the direct use of natural inducible promoters toward engineered regulatory systems that integrate promoter remodeling, transcription factor engineering, computational design, high-throughput screening, and direct-acting promoter screening. This review systematically outlines recent progress in engineered chemically inducible gene regulatory systems, while maintaining a particular focus on promoter-centered design, focusing on five core design principles, including orthogonality, reversible responsiveness, dose dependence, modular compatibility, and sequence-dependent structural regulation. We highlight emerging strategies such as AI-driven promoter prediction, direct-acting DNA-based switches (G-quadruplex systems), and engineered receptor pathways that expand chemical sensing beyond classical transcription factors. Furthermore, we examine cutting-edge applications in metabolic pathway optimization, precision gene therapy, biosensor development, and programmable synthetic circuits, illustrating how chemically inducible promoters enable context-aware biological control. Despite challenges related to inducer permeability, cross-talk, and scalability, future progress is anticipated through the development of trace-free inducers, AI-assisted orthogonal system design, and autonomous regulation strategies for industrial scalability. Together, these advances establish chemically inducible promoters as foundational components of next-generation synthetic biology, bridging chemistry, computation, and engineering to drive innovations in biomanufacturing, therapeutics, and intelligent cellular systems.
    Keywords:  Biosensors; Chemically inducible gene regulatory systems, Promoters; Engineered genetic switches; Gene expression regulation; Synthetic biology
    DOI:  https://doi.org/10.1016/j.biotechadv.2026.108963
  46. Sci Rep. 2026 Jun 30.
    An open-source 3D printing system enabling in-situ freeze-thaw processing of hydrogels.
    Guangteng Zhang, Yadong Chen, Meichen Wang, Da Ge, Qiang Du, Li Ke, Tianxing Gong, Feng Qi, Juncheng Bao.
      Hydrogels are widely used in tissue engineering and scaffold fabrication due to their excellent biocompatibility, while 3D printing excels at creating complex architectures. Among various techniques, low-temperature extrusion-based 3D printing has shown promise for hydrogel scaffold fabrication, as rapid solidification under controlled cooling can improve shape retention during deposition. However, commercial low-temperature DIW systems are often expensive, closed-source, and difficult to customize. Moreover, most require a two-step post-processing workflow involving external freeze-thaw cycles, which can damage structures through mechanical disturbance and temperature gradients, increasing contamination risk. To address these issues, we developed a low-cost, open-source low-temperature 3D printing platform by modifying a commercial FDM printer with custom hardware and upgraded software. It maintains stable - 30 °C ± 1 °C and supports in-situ freezing and freeze-thaw processing. Using a Poly(vinyl alcohol)-lignosulfonate sodium-TEMPO-oxidized cellulose nanofibrils (PVA-LS-TOCNF) hydrogel as the model ink, we achieved stable printing of various patterns and mechanical test specimens, with tensile properties comparable to those from ex-situ freeze-thaw methods. Overall, this platform significantly lowers barriers to low-temperature hydrogel 3D printing and improves accessibility.
    Keywords:  Hardware; Hydrogels; Low-temperature 3D printing; Software
    DOI:  https://doi.org/10.1038/s41598-026-60330-2
  47. bioRxiv. 2026 Jun 17. pii: 2026.06.16.731623. [Epub ahead of print]
    Label-Free All-Electrical Tracking of Individual and Collective Cell Migration on a Megapixel CMOS Capacitance Sensor.
    Hyuntae Jeong, Pushkaraj Joshi, Yinshi Hu, Jiwon Kim, Anh Hoang Vu, Jacob K Rosenstein, Ian Y Wong.
      Label-free tracking of adherent cell migration could enable important insights into biological processes such as tissue repair, inflammatory response, or cancer progression. Nevertheless, visualizing unlabeled animal cells using optical microscopy remains challenging due to low contrast as well as frequent changes in cell shape and number. A promising alternative uses electrical capacitance measurements, which are sensitive to cell adhesion to electrode surfaces. However, prior examples often utilized electrodes with areas larger than single cells, resulting in averaged readouts over multiple cells. Here, we demonstrate label-free, live-cell tracking using a capacitance sensor array with more than 1 million pixels on a 10 micron pitch across an area larger than 1 square centimeter. We show that single cell morphology can be clearly segmented, and then used to reconstruct migration and proliferation dynamics using optical flow. We further track the spreading of multicellular spheroids, revealing fast-moving peripheral regions led by a collective leader cell "front." Finally, we demonstrate label-free imaging of millimeter-scale honeycomb-shaped tissues without the multi-image stitching often required for conventional microscopy. We utilize mutual capacitance measurements with electrically-programmable electrode spacing to reconstruct topographical features of these engineered tissues. Overall, CMOS capacitance imaging arrays enables label-free imaging spanning from single cells to large tissues, in a portable and scalable format for settings where optical microscopy may be difficult to access.
    DOI:  https://doi.org/10.64898/2026.06.16.731623
  48. Macromol Rapid Commun. 2026 Jul 01. e70351
    Designing Thermally Stable DNA Hydrogels via Entropically-Driven Acridine Intercalation.
    Shaina M Hughes, Amy M DiVito, Patrick F Strobel, Pearson J J Franz, Matthew E Currier, Nathan J Oldenhuis.
      Physically cross-linked hydrogels formed through supramolecular interactions typically relax more rapidly upon heating because reversible bond formation is often exothermic. In contrast, entropy-dominated associations can generate materials that maintain or strengthen mechanical properties with temperature. However, strategies to systematically tune entropy-driven behavior in polymer networks remain limited. Here, we investigate how environmental variables regulate reversible cross-linking in acridine-based DNA-intercalating supramolecular hydrogels (Acr-PEG DISHs). Hydrogels composed of 50 mg mL- 1 DNA and 4 mM bis-intercalating cross-linker were evaluated across buffer compositions with ionic strengths of I ≈ 0.004-0.17 M, salt concentrations from 0-0.75 M, different ion identities, and varied pH. Increasing ionic strength produced more elastic networks with slower relaxation dynamics, increasing relaxation times from ∼30-100 s in low-ionic-strength buffers to ∼55-625 s in PBS. At elevated salt concentrations (∼0.5 M), electrostatic screening dominated network behavior and increased transition state entropy by Eyring analysis. Although monovalent salts produced similar elastic responses, ion identity modulated dissociation kinetics (Na+< Li+< K+), whereas multivalent ions destabilized the network. In contrast, pH-dependent studies showed only minor effects because citrate-phosphate ionic strength masked acridine protonation. These findings identify the ionic environment as a powerful handle for tuning entropy-driven supramolecular hydrogel dynamics.
    Keywords:  DNA intercalation; DNA‐based hydrogels; DNA‐ion interactions; acridine intercalators; entropy‐driven assembly; supramolecular hydrogels
    DOI:  https://doi.org/10.1002/marc.70351
  49. Nat Commun. 2026 Jun 30.
    Engineering Rhodotorula toruloides as a platform organism for de novo synthesis of fatty-acid esters.
    Junyang Wang, Yang Zhang, Baisong Tong, Qiongyu Meng, Kai Yuan, Zhihui Wang, Dengbin Li, Yufeng Guo, Zongjie Dai, Zihe Liu, Huimin Zhao, Shuobo Shi.
      Fatty acid esters are building blocks in next-generation biofuels, eco-friendly detergents, crop-enhancing adjuvants, and high-value cosmetic emollients. However, their industrial production relies on two unsustainable approaches: petrochemical-derived chemical catalysis that poses sustainability challenges and botanical extraction processes that exacerbates land-use conflicts. Here we develop a de novo microbial biosynthesis platform using the non-conventional oleaginous yeast Rhodotorula toruloides as a chassis, and achieve high-level biosynthesis of structurally diversified esters without the addition of alcohol or lipid precursors. By screening specific pathway enzymes and conducting modular pathway engineering, we successfully reprogram the native lipogenic metabolism of R. toruloides for de novo synthesis of fatty acid ethyl esters (FAEEs) at 579 mg/L, fatty acid short-branched chain esters (FASBEs) at 169 mg/L, and wax esters (WEs) at 1.30 g/L in shake-flask fermentation. As a case study, we optimize the synthesis of WEs in a 5 L fermenter, and achieve a production of 13.04 g/L. These engineered strains potentially offer an efficient, economical and environmentally friendly platform for the industrial production of fatty acid esters and oleochemicals.
    DOI:  https://doi.org/10.1038/s41467-026-75029-1
  50. ACS Appl Mater Interfaces. 2026 Jun 29.
    Beyond the 2D Plane: Interfacing Microwave Resonators with Bioreceptor-Functionalized Hydrogel Micropillars for Label-Free Enhanced Sensitivity Biosensing.
    Ghanimah N Abuhaimed, Haoliang Lu, Apala Banerjee, Jorge Romero Dominguez, Erol Hasan, Atif Shamim, Dana Z Alsulaiman.
      Facile and quantitative detection of liquid biopsy biomarkers such as microRNAs offers significant potential for precision healthcare; however, conventional biosensing methods rely on enzyme- or label-based workflows that are costly, time-consuming, and labor intensive. Microwave biosensors, particularly split-ring resonators (SRRs), offer an attractive alternative as they enable label-free, noncontact electromagnetic detection through permittivity measurements and are compatible with printed-circuit-board manufacturing. However, the sensitivity of conventional SRR platforms remains insufficient for clinically relevant biomarker detection. Here, we introduce an enzyme-free, label-free microwave biosensing architecture that integrates SRRs with microfluidic channels containing localized bioreceptor-functionalized hydrogel micropillars. Target hybridization within the hydrogel micropillars induces localized changes in complex permittivity, which are transduced into concentration-dependent shifts in the resonant frequency of the SRR capacitive gap. As a proof of concept, the platform is applied to detect the cancer-associated biomarker miR-16-5p using peptide nucleic acid (PNA) probes, which were selected for their neutral backbone, enzymatic stability, and strong hybridization affinity. The hydrogel micropillars act as three-dimensional scaffolds that enhance probe loading and maximize volumetric electromagnetic interaction, representing a departure from conventional planar biointerfaces. Compared with equivalent planar systems, this architecture achieves approximately a 20-fold improvement in detection limit, reaching subnanomolar sensitivity without any amplification or labeling while maintaining single-nucleotide specificity and strong device reproducibility. Beyond being the first demonstration of SRR-based miRNA detection, this work establishes a general strategy for three-dimensional microwave biosensing and positions hydrogel-interfaced resonators as a next-generation platform for sensitive, selective, label-free, and reusable biosensors.
    Keywords:  hydrogels; label-free sensing; microRNA; microwave biosensors; peptide nucleic acids; reusable biosensor; split ring resonators
    DOI:  https://doi.org/10.1021/acsami.6c03692
  51. iScience. 2026 Jul 17. 29(7): 116425
    Mitochondrial-generated G-quadruplex-forming lncRNAs regulate heme homeostasis.
    Vinodh J Sahayasheela, Ryohei Noizumi, Manendra B Lankadasari, Takumi Terada, Mitsuharu Ooga, Atharv Kulkarni, Shinjiro Suzuki, Takuya Hidaka, Li Cai, Ganesh N Pandian, Toshikazu Bando, Amit R Reddi, Hiroshi Sugiyama.
      Heme is an essential but potentially toxic prosthetic group synthesized in mitochondria. Maintaining mitochondrial heme homeostasis requires precise regulation of labile heme availability. Here, we show that mitochondria-generated long non-coding RNAs (mt-lncRNAs) are enriched in G-quadruplex-forming sequences and that these RNA G-quadruplex (rG4) structures bind and buffer heme. Using G4-specific pull-down and bio-orthogonal imaging, we demonstrate rG4 formation in mt-lncRNAs inside cells and show that mt-lncRNA rG4s bind hemin in vitro. Using orthogonal chemical perturbations-a mitochondria-targeted pyrrole-imidazole polyamide (MITO-PIP), which depletes mt-lncRNAs by inhibiting L-strand transcription, and MITO-pyridostatin derivative (MITO-PyPDS), which competitively displaces heme from rG4 structures-combined with genetically encoded heme sensors and ρ0 cells, disrupting mt-lncRNA rG4s increased labile mitochondrial heme, elevated nuclear and cytoplasmic heme, induced reactive oxygen species, and upregulated heme oxygenase 1 (HMOX-1). These findings establish an RNA structure-based mechanism for organellar metabolite buffering, with implications for heme-related disorders and mitochondrial disease.
    Keywords:  biochemistry; biophysics; molecular biology
    DOI:  https://doi.org/10.1016/j.isci.2026.116425
  52. ACS Appl Mater Interfaces. 2026 Jul 02.
    Enzymatically Polymerized Glycolated Conductive Polymers as Soft Electrodes for Neural Bioelectronic Interfaces.
    Luigi Fabiano, Tobias Abrahamsson, Ludovico Aloisio, Rémy Cornuéjols, Donghak Byun, Grazia Maria Lucia Messina, Xenofon Strakosas, Daniel T Simon, Magnus Berggren, Chiara Musumeci.
      Organic bioelectronics relies on materials capable of efficiently transducing signals between ionic biological environments and electronic devices. Conducting polymers are particularly attractive for this purpose due to their mixed ionic-electronic conductivity, mechanical compliance, and chemical tunability. Among them, bis-ethylenedioxythiophene-thiophene (ETE)-based polymers can be synthesized in situ via mild enzymatic reactions, enabling seamless and substrate-free integration with biological systems. Here, we investigate the impact of hydrophilic side-chain engineering on the physicochemical, electrochemical, and biological properties of ETE-based polymers by comparing two polymers which differ only by the presence of a triethylene glycol side chain between the ETE core and the terminal carboxylic group. We show that glycolation leads to increased film hydration and surface roughness without a measurable change in elastic modulus, suggesting competing effects from molecular ordering and ionic cross-linking. In a neuronal cell model, the glycolated polymer exhibits markedly enhanced cytocompatibility and cell adhesion, likely driven by its increased surface roughness and matrix topography. By combining electrochemical quartz crystal microbalance with dissipation monitoring, in-operando UV-vis spectroscopy, and electrochemical atomic force microscopy, we correlate ionic transport, swelling behavior, and nanomechanical responses, revealing enhanced electrochemically induced swelling in the glycolated polymer. Finally, when implemented as active channel materials in organic electrochemical transistors, both polymers display comparable performance, although the glycolated polymer shows slightly reduced cycling stability. These findings highlight the complex trade-offs introduced by side-chain glycolation and provide design guidelines for enzymatically synthesized conducting polymers in bioelectronic interfaces.
    Keywords:  ETE-based polymers; electrochemical swelling; enzymatic polymerization; glycolated conducting polymers; nanomechanics; neural biointerfaces; organic electrochemical transistors; organic mixed ionic−electronic conductors
    DOI:  https://doi.org/10.1021/acsami.6c07522
  53. J Am Chem Soc. 2026 Jul 02.
    Photoregulated Structural Memory in Supramolecular Polymers.
    Franziska Helmrich, Alejandro Martínez-Manjarrés, Antonia Albers, Mario Valverde, Olivier Galangau, Gustavo Fernández.
      Memory is a central principle underlying adaptive behavior in biological systems and an important source of inspiration for the design of functional artificial materials. While memory effects have been widely realized in macroscopic materials and devices, whether comparable behavior can arise from dynamic molecular organization remains largely unexplored. In supramolecular polymers (SPs), memory has thus far been demonstrated primarily in the form of chiral memory, while other types of memory, such as structural memory─where supramolecular organization is retained despite changes at the molecular level─remain largely unexplored. Here, we demonstrate structural memory in SPs through light-driven control over self-assembly pathways. We introduce a photoswitchable dithienylethene-based molecular building block capable of reversible interconversion between open- and closed-ring isomers both in the monomeric and assembled state. Although both isomers undergo supramolecular polymerization into elongated one-dimensional fibers in methylcyclohexane, they differ markedly in their aggregation propensity and resulting morphology (rigid, bundled fibers for the open form vs flexible, individual fibers for the closed form). By controlling the sequence of photoirradiation and supramolecular polymerization, we obtain pathway-dependent supramolecular architectures that retain features of their formation history despite changes at the molecular level. These results establish a route toward SPs capable of storing pathway information and advance the design of history-dependent adaptive soft matter.
    DOI:  https://doi.org/10.1021/jacs.6c05869
  54. bioRxiv. 2026 Jun 23. pii: 2026.06.20.733538. [Epub ahead of print]
    Particle-Only gECM Wafers Enable Cohesive, ECM-Rich Scaffolds Without Secondary Polymers.
    Shannon A Blanco, Juliet O Heye, Stephanie E Schneider, Maxwell C McCabe, Michael Floren, Corey P Neu.
      Granular extracellular matrix (gECM)-based biomaterials commonly contain polymer components to improve scaffold cohesion and handling during fabrication and use. However, these polymer hydrogel components may dilute ECM content and increase fabrication and regulatory complexity. This study evaluated whether particle-only gECM wafers could serve as a simplified alternative to hydrogel-based gECM scaffolds while maintaining structural, mechanical, and biological performance. Decellularized human cartilage and skin tissues were processed and fabricated into three scaffold formats: gECM hydrogels, freeze-dried gECM hydrogel wafers, and freeze-dried particle-only gECM wafers. Across fabrication methods, scaffold swelling, volume fraction, and stiffness were strongly influenced by both tissue type and fabrication approach. gECM hydrogels exhibited the greatest swelling and lowest stiffness, while gECM wafers displayed higher volume fractions and greater mechanical stiffness. Notably, gECM particle-only wafers achieved performance comparable to gECM hydrogel wafers despite the absence of a secondary polymer network. Particle-only wafers also maintained swelling behavior and structural properties over 3 months of dry storage at room temperature, with only modest decreases in stiffness. In vitro studies showed sustained cell viability over 14 days on particle-only wafers, with chondrocytes infiltrating cartilage wafers and fibroblasts remaining primarily surface-localized on skin wafers. In addition, particle-only wafers remained cohesive during implantation into a bovine cartilage defect model. These findings demonstrate that particle-only gECM wafers can achieve structural integrity, mechanical performance, and cytocompatibility without the need for an additional polymer network, highlighting a simplified and ECM-rich biomaterial platform. By eliminating polymer carriers and enabling dry storage with preserved function, this approach supports the development of off-the-shelf, translationally accessible gECM particle-only wafers for tissue engineering applications.
    DOI:  https://doi.org/10.64898/2026.06.20.733538
  55. Adv Mater. 2026 Jul 01. e73787
    Impact-Resistant Hydrogels Via Quaternary Ammonium-Regulated Networks.
    Xingkui Guo, Binxin Dong, Shuangshuang Miao, Chuyang Chen, Lingyi Hong, Wei Zhai.
      Hydrogels are increasingly explored as structural candidates for impact-mitigation and protection systems because of their biocompatibility, softness, and design versatility. However, conventional hydrogels typically suffer from inadequate mechanical properties and environmental instability, which severely hamper their practical applications. Here we report the use of quaternary ammonium-regulated networks to overcome these limitations, without the need for cumbersome postprocessing or high energy consumption. The approach enables controlled structural organization in polymers containing regularly spaced polar groups (e.g., polyvinyl alcohol, poly(acrylic acid), and polyacrylamide), transforming large, densely packed rigid domains into dynamic, adaptable supramolecular architectures. This arises from strong quaternary-ammonium-polymer associations that restrict local chain mobility and promote ordered segmental packing. Consequently, by tuning polymer composition, the hydrogels have widely tunable mechanics from brittle to ductile behavior, with ultimate stresses of 32.9-101.9 MPa, strains of 29%-1670%, and toughness values of 22.7-434.1 MJ m- 3. They also show exceptional impact-resistant performance (426.7 MPa), combined with high energy dissipation (96.02%) and puncture resistance (1.3 J), which compares favorably to those of other tough hydrogels and even natural materials. The presented strategy is generalizable to other polymers, and could expand the applicability of structural hydrogels to more mechanically demanding conditions.
    Keywords:  hydrogen‐bond‐associated domain; impact protection; ion‐dipole interaction; quaternary ammonium; structural hydrogels
    DOI:  https://doi.org/10.1002/adma.73787
  56. Proc Natl Acad Sci U S A. 2026 Jul 07. 123(27): e2606412123
    Beyond unit cells: Programmable morphogenetic design of irregular architected materials.
    Hailin Deng, Qingkun Zhao, Taishan Liu, Zhenghao Zhang, Zelin Zhu, Yanqi Zhou, Hua-Xin Peng, Wei Yang, Huajian Gao, Haofei Zhou.
      Architected materials derive functionality from geometry, yet conventional unit cell-based design limits functional heterogeneity, geometric adaptability, and robustness to defects. Inspired by natural morphogenesis, we introduce RDGenCAD, a morphogenetic design framework that translates programmable growth rules into reaction-diffusion dynamics to generate self-organized, CAD-ready architectures. A database of 120,000 morphogenetic structures reveals statistically deterministic and continuous tunability of elastic properties across auxetic and conventional regimes, despite pronounced geometric irregularity. These architectures further exhibit emergent flaw insensitivity and crack deflection through stress compartmentalization, leading to synergistic gains in strength and toughness relative to regular lattices. By shifting architected material design from unit-cell tessellation to programmable morphogenetic growth, this work establishes self-organization as a generative principle for designing materials that are irregular yet predictable, heterogeneous yet "coherent," and directly manufacturable.
    Keywords:  architected materials; defect tolerance; morphogenetic design; reaction–diffusion; self-organization
    DOI:  https://doi.org/10.1073/pnas.2606412123
  57. Adv Sci (Weinh). 2026 Jun 29. e76042
    CREAT: A CRISPR-Based Genome Trimming Strategy for Systematic Identification of Dispensable Regions and Rapid Genome Reduction.
    Guanhua Yuan, Zhe Gao, Yingxuan Qi, Yang Zhang, Xuhui Tian, Pengpeng Zhao, Xu Feng, Qunxin She.
      The construction of minimal-genome microbes offers an ideal platform for understanding fundamental biological processes and synthetic biology, yet the research is hindered by incomplete lists of essential genes in microbes and by multiple rounds of genome trimming with a trial-and-error nature. To address this, we introduce CREAT (CRISPR-based genome trimming with a multi-homology-arm template)-a streamlined approach that integrates CRISPR-targeted genome cleavage and homology arm walking to classify essential from non-essential genomic subregions, thus providing the basis for predicting essential genes in a given organism. These essential genes were then assembled into synthetic gene cassettes for one-step replacement of the targeted non-deletable genomic regions for further genome trimming. Eight consecutive rounds of CREAT genome trimming achieved a 20.8% reduction in genome size in Saccharolobus islandicus. Furthermore, Cas9-based CREAT genome trimming was developed for Bacillus subtilis and Escherichia coli, with efficiency greatly enhanced by the λ-Red recombinase in the latter. Together, this iterative application of CREAT provides a scalable and generally applicable strategy for rapidly constructing minimal genomes across diverse microorganisms.
    Keywords:  CRISPR‐Cas; classification of essential vs. nonessential regions; genome reduction; multi‐homology arms; synthetic genomic fragments; λ‐Red
    DOI:  https://doi.org/10.1002/advs.76042
  58. Nat Commun. 2026 Jul 02.
    Intracellular assembly of artificial enzymes for cytoplasmic enantioselective Mannich reactions.
    Zhixi Zhu, Qinru Hu, Yao Wu, Binju Wang, Zhi Zhou.
      Artificial enzymes constructed by introducing abiological catalytic cofactors into protein scaffolds are emerging as promising biocatalysts for reactions that have no natural equivalents. However, the design of artificial enzymes for in cellulo stereoselective biosynthesis remains largely unexplored because of the numerous challenges posed by the complex cellular environment. Here, we present an efficient strategy for the intracellular assembly of artificial enzymes via covalent anchoring by incubating cells that are expressing target protein with a synthetic catalytic cofactor, in the manner of natural enzymes. The artificial enzyme is assembled efficiently via site-specific disulfide-bond formation in cells, and it catalyzes an asymmetric Mannich reaction in cellulo with excellent enantioselectivity and reactivity. Crystallographic analysis combined with computational studies provides structural and mechanistic insight into the stereoselectivity and catalytic proficiency. Overall, this work establishes a versatile and generalizable approach to construct artificial enzymes in cellulo, expanding the toolkit for tailored synthetic applications in cellular contexts.
    DOI:  https://doi.org/10.1038/s41467-026-75059-9
  59. Nature. 2026 Jul 01.
    As transistors get smaller, electrodes must keep shrinking too.
    Bent Weber.
      
    Keywords:  Electrical and electronic engineering; Materials science; Technology
    DOI:  https://doi.org/10.1038/d41586-026-01807-y
  60. Adv Mater. 2026 Jun 30. e73815
    Composite Liquid Marble Templated Millimetric Capsule With Tunable Rigidity, Porosity, and Thermal Reconfigurability Toward 3D Cell Culture.
    Chittaranjan Mishra, Debasmita Sarkar, Chitra Jaiswal, Anuradha Kirtonia, Sumit Sarkar, Saurav Kumar, Mizuki Tenjimbayashi, Biman B Mandal, Uttam Manna.
      The extensive reliance on animal models in biomedical research motivates the development of advanced in vitro systems that recapitulate physiological complexity while minimizing animal use. Large cellular spheroids can mimic native tissue architecture; however, scalable fabrication of spheroids exceeding millimeter dimensions remains challenging. Here, we introduce a rigid porous capsule (RPC) in millimeter scale, a mechanically robust yet highly permeable platform that imposes external geometric confinement to enable cell-cell aggregation and three-dimensional proliferation. The RPC is fabricated by thermally processing LMs composed of a binary mixture of superhydrophobic particles: meltable poly(octadecyl acrylate) (PODAc) microparticles and non-meltable bovine serum albumin (BSA) nanoparticles. Selective melting of PODAc induces a transformation of the initially fragile, porous LM shell into a rigid and macroporous architecture (pore size in µm scale). By modulating the binary mixture composition, the shell stiffness and porosity are precisely tuned to balance mechanical stability with efficient nutrient transport. The resulting RPCs retain a highly spherical geometry and support 3D cell culture for at least 14 days, enabling the formation of viable, scaffold-free spheroids on a millimetric scale. This RPC establishes a physiologically relevant system for advanced tissue modeling and drug screening.
    Keywords:  3D cell culture; composite Liquid marble; phase transition; porous capsules; spheroid; superhydrophobicity
    DOI:  https://doi.org/10.1002/adma.73815
  61. Trends Biochem Sci. 2026 Jul 02. pii: S0968-0004(26)00179-9. [Epub ahead of print]
    A metabolon channels nicotine biosynthesis.
    Hao Zhang, Benke Hong.
      A recent study by Chang et al. uncovers a series of cryptic glycosylated intermediates and previously elusive enzymes that complete the nicotine biosynthesis. They demonstrate that nicotine biosynthetic enzymes and a transporter assemble into a vacuolar membrane metabolon that enables substrate channeling, enhances pathway efficiency, and promotes nicotine accumulation.
    Keywords:  biosynthesis; metabolic engineering; metabolite channeling; metabolon; nicotine
    DOI:  https://doi.org/10.1016/j.tibs.2026.06.003
  62. Metab Eng Commun. 2026 Dec;23 e00283
    Transcriptional regulatory network differences between six industrial Escherichia coli strains.
    Yuan Yuan, Gaoyuan Li, Ying Hefner, Richard Szubin, Jaemin Sung, Irina Rodionova, Bernhard O Palsson.
      Escherichia coli strains are widely used across numerous industrial and biotechnological applications. Yet their performance varies substantially in ways that can not be anticipated from genome annotation. Because transcriptional regulatory networks (TRNs) govern cellular functions such as motility, stress responses, metabolic flexibility, and production efficiency, differences in TRN organization and use may underlie many observed phenotypic differences. To investigate TRN differences between strains, we generated a compendium of 433 matched RNA-Seq profiles for six commonly used industrial E. coli strains (BL21, C, Crooks, MG1655, W, and W3110) and applied iModulon analysis to compare the state of their TRNs under similar growth conditions. This analysis revealed that core regulatory programs with similar functions are wired differently across the strains, and that the strains engage these programs in distinct ways when exposed to the same environmental challenges. Together, these findings highlight transcriptional regulation diversity underlying phenotypic expression among industrial E. coli strains. By providing an integrated view of TRN differences across widely used hosts, this work offers a fundamental basis for interpreting strain-specific behaviors and supports more informed approaches to strain selection and optimization.
    DOI:  https://doi.org/10.1016/j.mec.2026.e00283
  63. Nat Struct Mol Biol. 2026 Jun 30.
    Genome-wide absolute quantification of chromatin looping.
    James M Jusuf, Jin H Yang, Jack Toppen, Simon Grosse-Holz, Michele Gabriele, Pia Mach, Ilya M Flyamer, Christoph Zechner, Luca Giorgetti, Leonid A Mirny, Anders S Hansen.
      Three-dimensional genomics methods such as Hi-C and Micro-C have uncovered chromatin loops across the genome and linked these loops to gene regulation. However, these methods only measure three-dimensional interaction probabilities on a relative scale. Here we overcome this limitation by using live-imaging data to calibrate Micro-C in mouse embryonic stem cells, thus obtaining absolute looping probabilities for 65,929 Micro-C-identified chromatin loops. We find that the looped state is generally rare, with a mean pairwise looping probability of 1.2% and a maximum of 25% across the quantified loops. On average, CTCF-CTCF loops are stronger than cis-regulatory loops (2.2% versus <1%). Our findings can be extended to human cells with available Micro-C data under certain assumptions. Overall, we establish an approach for genome-wide absolute loop quantification and report that loops occur with low probabilities, generalizing recent live-imaging results to the whole genome.
    DOI:  https://doi.org/10.1038/s41594-026-01819-2
  64. Cell Syst. 2026 Jun 29. pii: S2405-4712(26)00135-3. [Epub ahead of print] 101653
    Scalable enumeration and sampling of minimal metabolic pathways for organisms and communities.
    Ove Øyås, Axel Theorell, Jörg Stelling.
      Many interactions in microbial consortia or tissues of multicellular organisms rely on networks of metabolite exchanges. To predict community function and composition beyond statistical correlations, one can use genome-scale metabolic models. However, comprehensive model analysis via metabolic pathways is a major challenge because pathway counts grow combinatorially with model size. Here, we define minimal pathways that yield compact representations of metabolic network capabilities. They generalize existing pathway concepts by allowing inhomogeneous constraints and targeted analysis of subnetworks, and we show how to enumerate and sample them efficiently via iterative minimization and pathway graphs. This enables applications such as assessing quantitative gene essentiality in the central metabolism of Escherichia coli, predicting metabolite exchanges associated with homeostasis and health in a host-microbe model of the human gut, and designing butyrate-producing microbial communities. Minimal pathways enable scalable analysis of metabolic subnetworks such as metabolite exchanges in uni- and multicellular systems. A record of this paper's transparent peer review process is included in the supplemental information.
    Keywords:  genome-scale metabolic network models; metabolic pathways; microbial communities
    DOI:  https://doi.org/10.1016/j.cels.2026.101653
  65. Nat Commun. 2026 Jul 02.
    Programmable one-pot polymerase-mediated DNA synthesis via temperature control.
    Jinho Kim, Jangho Choi, Woojin Kim, Namjin Cho, Yushin Jung, Seongjun Park, Eunjin Choi, Chaerim Lee, Youngeun Kim, Taehoon Ryu, Hansol Choi, Yeongjae Choi.
      Polymerase-mediated DNA synthesis is fundamental to numerous biotechnology applications, but existing programmable synthesis methods depend on exchanging DNA building blocks, thereby increasing reagent use and complicating multistep workflows. Here, we introduce the TEmperature Mediated Primer Exchange Reaction (TEMPER), a programmable platform for arbitrary DNA synthesis that operates solely through temperature control without solution exchange. TEMPER uses hairpin DNA as temperature-responsive building blocks that define specific temperature range for DNA synthesis. The temperature range is determined by the length design of the hairpin, which regulates thermodynamic interactions between DNA molecules and allows selective and sequential DNA synthesis in one-pot. We validate its versatility by developing a DNA data storage writer, a colorimetric temperature indicator, and a temperature data logger, highlighting its broad potential in nanotechnology and biotechnology applications.
    DOI:  https://doi.org/10.1038/s41467-026-74890-4
  66. Nat Food. 2026 Jul 03.
    Artificial intelligence for food innovation.
    Bianca Datta, Markus J Buehler, Yvonne Chow, Kristina Gligorić, Dan Jurafsky, David L Kaplan, Rodrigo Ledesma-Amaro, Giorgia Del Missier, Lisa Neidhardt, Karim Pichara, Benjamin Sanchez-Lengeling, Miek Schlangen, Skyler R St Pierre, Ilias Tagkopoulos, Anna Thomas, Nik Watson, Ellen Kuhl.
      Global food systems must deliver nutritious, sustainable foods while sharply reducing environmental impact. Yet, food innovation remains slow, empirical and fragmented. Artificial intelligence (AI) offers a transformative path to link molecular composition to functional performance, connect chemical structure to sensory outcomes and accelerate cross-disciplinary innovation across the production pipeline. While it is broadly applicable to food systems, we focus on sustainable proteins-plant-based, fermentation-derived and cultivated-as a high-impact test bed for AI-driven closed-loop design. We review the applications, opportunities and challenges of AI for food as an emerging discipline that integrates ingredient design, formulation development, fermentation and production, texture analysis, sensory science, manufacturing and recipe generation. We identify four priorities: advancing scientific machine learning with embedded domain priors, treating food as a programmable biomaterial, building self-driving laboratories for automated discovery and developing deep reasoning models that integrate nutrition and sustainability. Integrating AI responsibly into the food innovation cycle can accelerate the transition to sustainable food systems and establish a predictive, design-driven science of food for human and planetary health.
    DOI:  https://doi.org/10.1038/s43016-026-01380-7
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