bims-enlima 2026-08-16 papers

bims-enlima

Biomed News

on Engineered living materials

Issue of 2026–08–16
38 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool

Beyond the golden rule of polymer network dynamics: Design principles for tissue-mimetic viscoelasticity.
Spatial Control of Light-Responsive Proteins and Optogenetics Within Hydrogels via Volumetric Bioprinting.
Nanoarchitectonics Approach for Hydrogel Surface Functionalization via Self-Assembly of Terminally Modified Cello-oligosaccharides.
Adhesive Protein Nanoparticles Control Emulsion Properties via Tunable Interdroplet Linking.
Mechanistic machine learning for prediction of prime editing outcomes.
A Skin-Inspired High-κ Self-Healing Polymer for Low-Voltage Dielectric Elastomer Actuators.
Insertion-Ligation Reconstitution of Transmembrane Proteins for Functional Interfaces in Synthetic Cells.
Starch granules are instructive scaffolds for synergistic reinforcement and dissipation in hydrogel composites.
Reversible, Chemically Triggered Water Retention in Disulfide Cross-Linked Synthetic Conserved Anterior Mucus Proteins (SCAMPs).
Fully Printed Ionic Diodes from Polymerizable Ionic Liquids.
Flip Flop-Associated Growth and Division of Synthetic Cells.
AI-assisted design of synthetic gene editors.
Photoactive Lignin-Derived Nanolayers for Camouflaged Bioaromatic Interfaces.
The phase-shifting architecture of chromosomes.
Self-Growing Conductive Hydrogels Establish Volumetric Biointerfaces for Cardiac Conduction Restoration.
Acoustic virtual walls enable open, scalable, and programmable microfluidics.
eFormate-mediated CO2 bioconversion: A modular electrochemical-microbial cascade compared across a diverse set of microorganisms.
Near Infrared-Programmed In Situ Mechanical Reconfiguration of Adhesive Hydrogels for Pressure Distribution Recognition.
A Multifunctional and Secure Photoresponsive Proteasome Inhibitor to Control Cell Fate.
N-cadherin peptides modulate integrin-mediated mechanosensing and preserve mesenchymal stem cell phenotype on tunable hydrogels.
Flax Composites With Improved Interfacial Strength Through Microbially Induced Mineral Precipitation.
Engineered probiotics block arsenite absorption in the gastrointestinal tract.
Microbiomics.
Molecular assembly as a universal biosignature measurable by mass spectrometry.
Nanopore-Based Profiling of PEGylation in Nucleic Acid Therapeutics.
Sequential stenciling to reconstitute 2D microtissues for multicellular and synthetic signaling architectures.
Decoding mechanoregulation in immunological synapses using biomimetic artificial cells.
Versatile Compartmentalization of Hydrogel-Medium Interfaces in Microfluidic Channels for Reconstructing Complex Tissue Architectures.
Yeast single-cell proteins from CO2 with tandem biological systems.
3D printable tough hydrogel actuators.
Structural mechanism governing the directionality of bridge recombination.
The history of enzyme evolution embedded in metabolism.
Single-exposure holographic 3D printing via inverse-designed phase masks.
Conductive and magnetic silk biomaterials: functionalization strategies and challenges for sustainable bioelectronics.
Polyamines buffer labile iron to suppress ferroptosis.
Bottom-up reconstruction of synthetic pyrenoids provides insights into the mechanisms and evolution of carbon concentration by EPYC1 proteins.
Metal Ion-Triggered Collapsed Hydrogels as Materials for Bacterial Population Control.
A modular platform for measuring substrate oxidation by CO2 production in diverse cell culture systems.

Sci Adv. 2026 Aug 14. 12(33): eaeg8172

Beyond the golden rule of polymer network dynamics: Design principles for tissue-mimetic viscoelasticity.

Emilie A Moses, Claire J Wang, Joseph Collins, Jessica Garcia, Josiah H Marshall, Andrey V Dobrynin, Sergei S Sheiko.

Technologies ranging from transportation to biomedical devices rely on soft materials whose performance hinges on balancing stiffness and damping. In conventional polymer networks, however, these properties are typically coupled: Softer materials are intrinsically more dissipative, reflecting a long-standing correlation in polymer dynamics that severely restricts the accessible design space. Here, we move beyond this longstanding constraint using brush-like polymer networks whose architecture in combination with chemistry governs viscoelastic response. By independently tuning strand volume and flexibility, we vary the elastic modulus over orders of magnitude while maintaining nearly constant relaxation time without altering network chemistry. Our findings establish a general framework for encoding viscoelastic responses in polymer networks, enabling the design of tissue-mimetic materials with programmable equilibrium stiffness and rate-dependent dissipation.

DOI: https://doi.org/10.1126/sciadv.aeg8172
Adv Mater. 2026 Aug 10. e74563

Spatial Control of Light-Responsive Proteins and Optogenetics Within Hydrogels via Volumetric Bioprinting.

Davide Ribezzi, Pere Català, Gabriel Größbacher, Paulina Nuñez Bernal, Olaf Nijssen, Sammy Florczak, Wilco Nijenhuis, Nuria Crusellas-Villorbina, Bram Nijhoff, Paul Delrot, Jos Malda, Andreas Hierholzer, Martin Fussenegger, Lukas C Kapitein, Riccardo Levato.

  Spatiotemporal control over cell fate and behavior within bioprinted constructs remains a key challenge in tissue engineering. Optogenetics offers versatile potential for non-invasive regulation of biological processes. Yet, its integration within large-scale, cell-laden bioprinted materials is still limited, especially considering the spatial constraints of existing light delivery methods. In this study, we introduce a novel approach that repurposes tomographic volumetric bioprinting to enable post-printing stimulation of photosensitive protein-switches and optogenetic circuits in cells deep within hydrogel constructs. By converging different bioprinting approaches, computer vision, context-aware model generation, and synthetic biology and cell engineering, we demonstrated selective activation of a fluorescent, light-responsive protein probe within multi-material centimeter-scale constructs. Moreover, leveraging a multi-wavelength volumetric bioprinter, we further demonstrate this concept by selectively stimulating cells expressing a near-infrared optogenetic system that triggers gene expression and the induction of pancreas-specific transcription factors. The described methods provide platforms for remote, repeatable, and localized control of biological events in volumetric constructs, opening new possibilities for advanced tissue models, and dynamic tuning of cell-mediated protein production in engineered living systems.

Keywords:  multi‐technology biofabrication; optogenetics; photosensitive proteins; synthetic biology; volumetric additive manufacturing

DOI:  https://doi.org/10.1002/adma.74563
ACS Polym Au. 2026 Aug 12. 6(4): 1223-1233

Nanoarchitectonics Approach for Hydrogel Surface Functionalization via Self-Assembly of Terminally Modified Cello-oligosaccharides.

Daniel Muara Sentosa, Hiroto Maruyama, Yuuki Hata, Kai Sugiura, Yu-Cheng Chiu, Takeshi Serizawa.

  Advances in hydrogel research have enabled the design of bulk networks with diverse functionalities; however, precise control of interfacial properties remains a key challenge to expanding their applications, particularly in biointerfaces. Here, we report a simple and versatile surface functionalization strategy based on the self-assembly of terminally modified cello-oligosaccharides. When azido-functionalized cello-oligosaccharides dissolved in 85% phosphoric acid are applied to hydrogel surfaces, mixing with the intrinsic water within the hydrogels induces rapid self-assembly, forming nanostructured granular coatings at the interface. This method is applicable to both chemically and physically cross-linked hydrogels. The resulting azido-functionalized surfaces enable postfunctionalization via click chemistry, allowing biomolecule immobilization. As a proof of concept, antigen-conjugated hydrogels were used for the detection of specific immunoglobulin G, exhibiting selective responses even in serum-containing environments due to the antibiofouling properties of the assemblies. These findings establish terminally modified cello-oligosaccharides as a new class of interfacial modifiers for hydrogels, providing a facile route to biofunctional and antifouling interfaces for sensing and diagnostic applications.

Keywords:  biomolecular sensing; cello-oligosaccharide; cellulose; hydrogel; self-assembly; surface functionalization

DOI:  https://doi.org/10.1021/acspolymersau.6c00076
Small. 2026 Aug 12. e75117

Adhesive Protein Nanoparticles Control Emulsion Properties via Tunable Interdroplet Linking.

Gijs D Konings, Ketan A Ganar, Emmanouil Chatzigiannakis, Elke Scholten, Constantinos V Nikiforidis.

  The mechanical properties of emulsions are governed by the ability of droplets to resist shear, making interdroplet connections crucial for tuning emulsion behavior. Here, we elucidate the mechanism by which dispersed oil droplets can be "glued" together using pea-protein nanoparticles that self-assemble through electrostatic interactions. We experimentally demonstrate the adhesive action of these nanoparticles across multiple length scales, using microfluidics, the thin film balance, confocal microscopy, and rheology, and explain the physical mechanism using theoretical models. Our results show that the nanoparticles simultaneously bind to two opposing droplet interfaces, forming electrostatically driven bridges that link droplets together. This adhesion dramatically transforms the mechanical response of the emulsion from a liquid-like material to a plastic-like, 3D-printable system, raising the storage modulus of emulsions from < 0.1 to 3.2 kPa. These insights highlight the potential of biosourced nanoparticles as a powerful tool for engineering emulsion mechanics via electrostatic forces, enabling applications that require materials with controlled mechanical properties, such as fat tissue mimetics or soft microelectronics.

Keywords:  3D printing; adhesive nanoparticles; interfacial rheology; microfluidics; thin film dynamics; tunable droplet linking

DOI:  https://doi.org/10.1002/smll.75117
Nat Biotechnol. 2026 Aug 12.

Mechanistic machine learning for prediction of prime editing outcomes.

Alvin Hsu, Peter J Chen, Angus H Li, Colin F Hemez, Xin D Gao, Markus Terrey, Charlie Nelson, Vijay Selvam, Ana Cristian, Amber N McElroy, Benjamin J Steinbeck, Gandhar K Mahadeshwar, Smriti Pandey, Zachary Barsdale, Paul Z Chen, Alexander A Sousa, Holt A Sakai, Rachel A Silverstein, Ilias Morad, Ryan K Krueger, Max W Shen, Benjamin P Kleinstiver, Cathleen M Lutz, Jakub Tolar, Bruce R Blazar, Mark J Osborn, David R Liu.

Prime editing (PE) can make specific local changes to genomic DNA in living systems but its efficient application currently requires extensive optimization of PE guide RNA (pegRNA) sequences. Here we present OptiPrime, a machine learning model of PE efficiency based on current understanding of PE mechanisms. OptiPrime achieves state-of-the-art accuracy on PE efficiency prediction and enables prediction of nicking guide RNA (PE3) and dual pegRNA (twinPE) outcomes. We validate that OptiPrime has learned the determinants of mammalian mismatch repair (MMR) and is well suited for nominating MMR-evasive silent edits that improve PE efficiency. We demonstrate the use of OptiPrime in a variety of prospective therapeutic contexts in primary human and mouse cells. Lastly, we show that OptiPrime can be used to achieve streamlined and efficient in vivo correction of a pathogenic mutation in the brain of a mouse model of KIF1A-associated neurological disorder. We provide a webserver for OptiPrime ( https://optipri.me/ ) as a community resource.

DOI: https://doi.org/10.1038/s41587-026-03261-7
Adv Mater. 2026 Aug 08. e23659

A Skin-Inspired High-κ Self-Healing Polymer for Low-Voltage Dielectric Elastomer Actuators.

Jian-Cheng Lai, Eunyoung Kim, Chengyi Xu, Simiao Niu, Yuanwen Jiang, Donglai Zhong, Yucan Peng, Weichen Wang, Zhitao Zhang, Christopher B Copper, Huaxin Gong, Hongping Yan, Yangju Lin, Deyu Liu, Chuanzhen Zhao, Can Wu, Yuelang Chen, Song Zhang, Yu Zheng, Gan Chen, Fuying Dong, Jeffrey B-H Tok, Zhenan Bao.

  Dielectric elastomer actuators (DEAs), known as a type of artificial muscles, are promising soft actuators with many applications including robotics and wearables due to their conformability, fast response, and large actuation. However, their usage remains constrained by high driving voltages needed to achieve substantial actuation. Here, we design a skin-inspired high-κ self-healing elastomer, poly-(acrylonitrile-co-butadiene)-co-thiourea (PABTU), that features a high dielectric constant (15 at 1 kHz), low Young's modulus (0.58 and 0.012 MPa upon pre-stretch), and ability to form pinhole-free thin films (∼ 3 µm). To mitigate relatively high dielectric loss of our PABTU, PABTU/PDMS-MPU0.3-IU0.7 bilayer structure (ULTRA) is used for actuators, increasing its breakdown strength from ∼33 to 43 V/µm. Our ULTRA actuators exhibit visible deformation at an unprecedented low voltage of 30 V and an areal strain exceeding 130% at 120 V, representing an order of magnitude reduction in voltage for actuation compared with previously reported DEAs while achieving similar actuation strain. As proof of concept, we demonstrate a low-voltage multipixel array with ULTRA DEA. Our molecular design concept provides a path for material systems toward low-voltage operating soft robotics.

Keywords:  dielectric elastomer actuators; high dielectric constant elastomers; self‐healing

DOI:  https://doi.org/10.1002/adma.202523659
Nano Lett. 2026 Aug 12. 26(31): 10091-10099

Insertion-Ligation Reconstitution of Transmembrane Proteins for Functional Interfaces in Synthetic Cells.

Alexander J Lin, Ahmed Z Sihorwala, Adithya Karthik, Amanda I Sobrinho, Yashapal Singh, Brian Belardi.

  In living cells, transmembrane (TM) proteins transduce extracellular cues across a lipid bilayer, a structure that is otherwise impermeable to high-molecular weight and charged molecules. Synthetic cells (SCs), lipid bilayer-based systems that offer complete control over composition and response, have emerged as attractive candidates for programmable transduction in biomedicine, sensing, and computing applications. However, SCs lack the complex machinery native to living cells that insert TM proteins into lipid membranes, limiting their potential for extracellular-to-intracellular transduction. Here, we present a two-step chemical method to reconstitute functional single-pass TM proteins in SCs, termed insertion-ligation. Using the insertion-ligation approach, we report reconstitution of SC-SC interfaces that transduce extracellular adhesion activity into intracellular organization and transmembrane complexes capable of signal transduction across the bilayer. Our chemical strategy enables the reconstitution of any single-pass TM protein in SCs, allowing researchers to access this functionally diverse class of proteins without the need for insertion machinery.

Keywords:  membrane interface; native chemical ligation; signal transduction; synthetic cell; transmembrane protein

DOI:  https://doi.org/10.1021/acs.nanolett.6c01025
Sci Adv. 2026 Aug 14. 12(33): eaef4627

Starch granules are instructive scaffolds for synergistic reinforcement and dissipation in hydrogel composites.

Shirlaine Juliano, Jasmine Samaniego, Ian M Lillie, Geraldine Ramirez, Peter M Iovine, Rae M Robertson-Anderson.

A fundamental challenge in soft material design is the competition between rigidity and dynamicity, as stiffening mechanisms typically suppress energy dissipation. Here, we demonstrate that starch granules serve as instructive scaffolds that overcome this constraint, enabling the synergistic amplification of both elastic reinforcement and dynamic dissipation in hydrogels. We show that engineering the charge and structure of the filler-matrix interface enhances this synergistic response, which we propose arises from a dual-action physical mechanism: Filler-induced polymer bundling of the polymer matrix provides structural reinforcement, while transient filler-matrix hydrogen bonding facilitates dissipation. Moreover, we reveal that binary blends of disparate filler species unexpectedly suppress these emergent properties, which we argue arises from enhanced entropic mixing. Our results provide a physical framework to overcome current design limitations in soft composites and sculpt their viscoelastic response from synergistic enhancement to strategic suppression for applications ranging from high-performance soft robotics to biomimetic tissue engineering.

DOI: https://doi.org/10.1126/sciadv.aef4627
Macromolecules. 2026 Aug 11. 59(15): 8607-8619

Reversible, Chemically Triggered Water Retention in Disulfide Cross-Linked Synthetic Conserved Anterior Mucus Proteins (SCAMPs).

Manuel A Lema, Chengyu Sun, Milan A Shlain, Farhana M Khan, Keidy L Matos, Seungri Kim, Vick Tan, Monil S Patel, Xi Chen, Adam B Braunschweig.

Water-responsive (WR) materials change their morphology and properties in response to variations in relative humidity (RH). Myriad biological processes, including lubrication, adhesion, and ion exchange, rely upon mucus hydrogels, the most prevalent, natural, WR material, and there is substantial interest in mucus hydrogels for biomedical and materials applications. The WR properties of mucus hydrogels arise from the structure of mucins, proteins with O-linked glycans on serine/threonine residues and cysteine (Cys)-mediated cross-linking. However, natural mucuses present significant challenges for materials and biomedical use because of their heterogeneity, instability, and limited scalability. As such, there is a need for synthetic materials that can recreate the structures and WR properties of their natural counterparts. We report a series of polymers, poly-(β-Gal-Thr) m -r-poly-(Cys-H) n , that are inspired by conserved anterior mucus proteins (CAMPs) found in snail mucus and that possess properties including water adsorption, stiffness, and effective work of adhesionthat are similar to natural mucus hydrogels and that are mediated by reversible, biomimetic disulfide cross-linking. The polymerization conditionsinvolving the ring opening of N-carboxyanhydride monomers to form glycosylated polypeptidesenables independent control over polymer length (m + n) and monomer ratio (m:n). The polymers were characterized by 1H NMR spectroscopy, mass spectrometry, and gel permeation chromatography, and all of the data are consistent with the proposed structures. The tunable mechanical and WR properties were measured using atomic force microscopy (AFM) and dynamic vapor sorption (DVS). Notably, as RH increases, the poly-(β-Gal-Thr) m -r-poly-(Cys-H) n polymers absorb water, with poly-(β-Gal-Thr)78-r-poly-(Cys-H)4 doubling in mass with hysteresis between the absorption and desorption profiles, indicative of a porous structure. Cross-linking to form poly-(β-Gal-Thr) m -r-poly-(Cys-D) n substantially decreases the water adsorption of the polymers, but the water adsorption can be reestablished by reducing the disulfide cross-links. These SCAMPs represent a significant step toward mimicking the complex structures and WR properties of natural mucus using synthetic analogs, and this work has implications for the design and implementation of synthetic mucus in biomaterials, biotechnology, and medicine.

DOI: https://doi.org/10.1021/acs.macromol.6c00640
ACS Nano. 2026 Aug 11. 20(31): 21953-21964

Fully Printed Ionic Diodes from Polymerizable Ionic Liquids.

Alexander Q Kane, Eric Yang, Ryan L Truby.

  Soft ionic diodes (SIDs) comprising p- and n-type polyelectrolytes are fundamental components of bioinspired iontronic devices. However, traditional ionic diode fabrication techniques require low-throughput, manual processes to interface electrodes and electrolytes and are typically limited to producing planar geometries. Moreover, hydrogels commonly used as SID electrolytes lose water over time, which leads to device instability and loss of performance. In this work, we present a method for fully 3D printing ionic diodes from solvent-free, polymerizable ionic liquids (pILs) that enables rapid and scalable manufacturing of SIDs. Four inks, including p- and n-type electrode and electrolyte inks, are used to print SIDs with 2D to 3D geometries and rectification ratios of up to 46. The geometry-, scan rate-, and time-dependent performance of SIDs are characterized via cyclic voltammetry and chronoamperometry. Leveraging the flexibility of 3D printing, we demonstrate current and voltage scaling relationships in multidiode arrays printed in parallel or series, respectively. We also highlight a dense multidiode crossbar array (≈100 SIDs/cm2) that can be quickly and uniquely achieved with our 3D printing approach. We anticipate the materials and methods reported in this work will enable opportunities for fabricating ionic diodes and multifunctional iontronic devices critical to advancing applications in bioelectronics, neuromorphics, and soft robotics.

Keywords:  3D printing; ionic diodes; iontronics; poly(ionic liquids); rectification

DOI:  https://doi.org/10.1021/acsnano.6c06135
ACS Nano. 2026 Aug 11. 20(31): 21723-21738

Flip Flop-Associated Growth and Division of Synthetic Cells.

Rafael B Lira, Marco Van Tilburg, Siewert J Marrink, Cees Dekker.

  Cells grow their boundaries by incorporating newly synthesized lipids into their membranes as well as through fusion of intracellular vesicles. As these processes yield trans-bilayer imbalances in lipid numbers, cells must redistribute lipids across the bilayer to enable sustained growth. Using giant and large unilamellar vesicles (GUVs and LUVs, respectively), we here recapitulate cellular growth and division under various conditions of transmembrane 'flip flop' of lipids. By dynamically monitoring the changes in reduced volume, spontaneous curvature, and area difference of GUVs that grow by fusion of many small LUVs, the morphology of these growing 'synthetic cells' is quantified. We demonstrate, for membranes containing various flip flop-capable molecules, that curvature stresses are relieved, generating more symmetrically sized buds, without significantly compromising the membrane integrity. Further increasing the neck curvature is shown to lead to bud scission. The mechanisms presented here offer insights into cell growth and division, which are important for understanding early protocells and designing synthetic cells that are able to grow and divide.

Keywords:  GUV; LUV; cell growth and division; flip flop; synthetic cells

DOI:  https://doi.org/10.1021/acsnano.6c03241
Nat Biotechnol. 2026 Aug;44(8): 1281

AI-assisted design of synthetic gene editors.

Dario Ummarino.

DOI: https://doi.org/10.1038/s41587-026-03273-3
ACS Appl Mater Interfaces. 2026 Aug 10.

Photoactive Lignin-Derived Nanolayers for Camouflaged Bioaromatic Interfaces.

Tam Thi-Thanh Huynh, Maarten Rubens, Marc Comí, Niko Van den Brande, Richard Vendamme.

  Bioaromatic polymers derived from lignin have largely been confined to bulk materials or dispersed (nano)particles, limiting their ability to control interfacial phenomena at the nanoscale. Here, we establish lignin as a platform for programmable photoactive bioaromatic nanolayers that form transferable interfaces across solid, liquid, and soft matter substrates. Depolymerized lignin is chemically functionalized and hybridized with a glycerol-derived triglycidyl ether to yield homogeneous bioresins that can be directly UV-cured into conformal nanoconfined networks. These coatings form nanometer- to micrometer-thick interfaces combining mechanical robustness, water repellency, and conformal integration across rigid substrates, elastomers, and hydrogels. The hybrid aromatic-aliphatic architecture enables both stiffness and conformability, supporting stable performance under deformation and in aqueous environments. Ultrathin confinement renders the inherently colored lignin network visually imperceptible under ambient light while preserving its interfacial functionality. The bioaromatic network exhibits intrinsic fluorescence without external dyes, enabling wavelength-dependent optical logic, invisible patterning, and light-addressable surface functions. This work establishes a general strategy to transform lignin into multifunctional interfacial nanomaterials, opening new opportunities for sustainable coatings, photonic surfaces, and multifunctional hydrated interfaces.

Keywords:  bioaromatic interfaces; intrinsic fluorescence; lignin upcycling; optical camouflage; optical patterning; photoactive bioresins; photopolymerization; transferable nanofilms

DOI:  https://doi.org/10.1021/acsami.6c08623
Science. 2026 Aug 13. 393(6812): 664-665

The phase-shifting architecture of chromosomes.

William Gelbart.

Mitotic chromosome size and shape are influenced by conditions that control ionic hydrogels.

DOI: https://doi.org/10.1126/science.aek0561
Adv Mater. 2026 Aug 10. e74527

Self-Growing Conductive Hydrogels Establish Volumetric Biointerfaces for Cardiac Conduction Restoration.

Fucheng Wang, Xingmei Chen, Ping Wen, Lingfeng Yuan, Yifan Yang, Zhipeng Ni, Pei Zhang, Xiaoyu Chen, Yuewen Zhang, Miao Cui, Ji Liu.

  Restoring three-dimensional electrical conduction in infarcted myocardium remains a critical challenge, as conventional conductive hydrogel patches largely remain surface-confined and prevent electrical coupling of residual cardiomyocytes within fibrotic scars. Here, we present a self-growing conductive volumetric interface (SCOVE) that transforms surface-confined biointerfaces into tissue-integrated, three-dimensional conductive networks. SCOVE is delivered as an injectable hydrogel precursor containing the tissue-permeable conductive monomer 3,4-ethylenedioxythiophene-acetic acid sodium salt (ETE), which rapidly infiltrates infarcted myocardium and undergoes endogenous glucose-triggered oxidative polymerization to self-grow a conductive polyETE network in situ. The resulting hydrogel gels within 1 min, reaches cardiac-mimetic conductivity (∼1 S m- 1) within 45 min, and preserves native myocardial mechanics without inducing tissue stiffening. In a rat myocardial infarction model, SCOVE penetrates the infarct, reduces scar resistivity by 2.54-fold compared with conventional 2D conductive patches, restores electrical coupling among residual cardiomyocytes, enhances Cx43 expression, and accelerates impulse propagation. By replacing static, surface-confined conductive patches with self-growing volumetric biointerfaces, this work establishes a generalizable strategy for reconstructing tissue electrophysiology and advancing bioelectronic therapies for myocardial infarction and other electrically dysfunctional tissues.

Keywords:  MI repairing; conductive hydrogels; self‐growing; three‐dimensional electrical conduction; volumetric biointerfaces

DOI:  https://doi.org/10.1002/adma.74527
Sci Adv. 2026 Aug 14. 12(33): eaec0104

Acoustic virtual walls enable open, scalable, and programmable microfluidics.

Hajin Oh, Mingyuan Liu, Tony Jun Huang, Junfei Li.

Microfluidic platforms are widely used across biomedical research, chemical synthesis, diagnostics, environmental monitoring, and materials science for precisely manipulating small volumes of fluids and suspended particles. However, conventional systems rely on narrow physical channels that are prone to clogging, limited volumetric throughput due to high hydraulic resistance, and excessive shear stress that can damage sensitive cells and fragile materials. To overcome these constraints, we introduce acoustic channeling within a wide, open fluid chamber by replacing solid boundaries with acoustic virtual walls. These walls are formed by evanescent acoustic pressure fields generated from an engineered two-dimensional waveguide that suppresses internal wave propagation and produces highly localized subwavelength fields. This architecture minimizes shear stress while guiding particles along precisely defined trajectories. The electronically tunable acoustic field enables programmable, remote, and real-time particle control. Supported by simulations, we demonstrate diverse channeling designs, efficient particle collection, and material-specific separation. Operating at milliliter-per-minute flow rates, two orders of magnitude higher than conventional microfluidic systems, this platform enables scalable, clog-free microfluidics for high-throughput and robust applications.

DOI: https://doi.org/10.1126/sciadv.aec0104
Proc Natl Acad Sci U S A. 2026 Aug 11. 123(32): e2608267123

eFormate-mediated CO2 bioconversion: A modular electrochemical-microbial cascade compared across a diverse set of microorganisms.

Jihoon Choi, Nicolas Grandel, Deepika Awasthi, Geonhui Lee, Abhishant Nigam, Yu Shan, Nathan E Soland, Maria Fonseca Guzman, Hye-Jin Jo, Diep N Pham, Peidong Yang, Blake A Simmons.

  Direct electrochemical CO2 reduction is currently limited to a narrow range of multicarbon products due to limited multicarbon pathways on Cu surfaces. Biochemical methods, by contrast, are often slow due to the slow rate of gas-liquid mass transfer to microbial cells. To overcome the limitations of the individual processes, integrating electrochemical systems with biosynthetic processes has become a promising approach. However, only a narrow range of microbial strains has been explored in these combined systems. Here, we introduce a modular abiotic-biotic platform that allows electrochemically produced formate (eFormate) to be supplied independently to various microbial systems. A concentrated formate solution (0.87 M) was produced within 4 h using a SnO2 catalyst and subsequently converted into a biocompatible carbon feedstock by adjusting the pH. Based on earlier reports, we identified and evaluated 13 microbial strains known to grow on formate, 10 of which exhibited robust growth in the prepared formate solution and successfully secreted multicarbon products and important metabolic markers like acetate, ethanol, lactate, pyruvate, and polyhydroxybutyrate (PHB). This work establishes a proof of concept for a broadly applicable abiotic-biotic platform that expands the microbial design space by coupling CO2 electrolysis with carbon upgrading.

Keywords:  CO2 conversion; abiotic–biotic; bioconversion; electrocatalysis

DOI:  https://doi.org/10.1073/pnas.2608267123
ACS Appl Mater Interfaces. 2026 Aug 17.

Near Infrared-Programmed In Situ Mechanical Reconfiguration of Adhesive Hydrogels for Pressure Distribution Recognition.

Zhenyi Wu, Xiaoyong Zhang, Fan Li, Xianglv Hu, Yang Wang, Wendi Liu, Jinmei He, Yongping Bai.

  Light driven soft actuators often struggle to integrate robust mechanical toughness, dynamic spatial tunability, and reliable on demand adhesion within a single material system. Here, we present a near infrared (NIR) light responsive hydrogel featuring dynamic noncovalent networks that enable the rapid and reversible reconfiguration of mechanical properties. The structural network integrates PVA chains to provide initial mechanical resilience and environmental durability, while the thermal responsive boronic ester bonds act as crosslinking junctions to ensure fast transition to a soft elastic state. This integrated architecture achieves a rare balance between high initial stiffness and on demand dynamic actuation, overcoming the long-standing trade off in responsive soft matters. Furthermore, the localized photothermal cleavage of the dynamic bonds exposes functional groups, which significantly enhances the interfacial adhesion to diverse surfaces, reaching approximately 48 kPa on aluminum. The localized photothermal reduction in mechanical stiffness endows the hydrogel with precise spatial control, enabling the design of untethered bionic actuators and interactive sensors. Beyond mechanical actuation, the hydrogel serves as a highly sensitive wearable electronic device, achieving precise human motion detection and Morse code communication. Furthermore, the integration of a 4 × 4 spatial pressure sensor array provides reliable tactile feedback for robotic manipulation tasks. This work highlights a versatile design strategy for programmable hydrogels, paving opportunities for smart interfaces, advanced human machine interaction, and adaptive soft robotic systems.

Keywords:  borate ester bonds; photothermal hydrogels; reversible adhesion; robotic perception; spatial tactile arrays

DOI:  https://doi.org/10.1021/acsami.6c12028
J Am Chem Soc. 2026 Aug 12. 148(31): 33698-33708

A Multifunctional and Secure Photoresponsive Proteasome Inhibitor to Control Cell Fate.

Manuel Valentin, David Féval, Sophia Borchert, Henry Dube, Esther Zanin.

Precise external control of biological processes represents a central interest in the life sciences. Specifically designed molecular tools are ideally suited for this purpose and consequently have found widespread applications including fundamental studies in biology or pharmaceutical drug development. Introducing photoresponsiveness to modulate the biological activity of a molecule offers heightened levels of control by adding adjustable spatial and temporal resolution. Here we present the next leap in capabilities in which the photoresponsiveness of a small molecule inhibitor is coupled to a customizable secondary function. This multifunctional photopharmacological tool is based on MG132─a potent proteasome inhibitor─whose activity is securely photocaged and thus rendered fully light-responsive. At the same time, an alkyne group is introduced into the structure allowing for facile late-stage attachment of a second functionality via simple click chemistry. The heightened utility is showcased by stably linking a fluorophore, allowing to monitor the spatial distribution of the photoactivatable inhibitor within living cells. This multilevel photoresponsive molecular tool opens up a vast space of opportunities for programmable and customizable biological activity control.

DOI: https://doi.org/10.1021/jacs.6c10586
Biomater Adv. 2026 Aug 06. pii: S2772-9508(26)00401-2. [Epub ahead of print]189 215102

N-cadherin peptides modulate integrin-mediated mechanosensing and preserve mesenchymal stem cell phenotype on tunable hydrogels.

Matthias Recktenwald, Hayley Jankowski, Tyler Torres, Sabriye Yilmaz, Matthew Lowe, Mohammed M Benmassaoud, Sebastián L Vega.

Mesenchymal stem cells (MSCs) are a clinically relevant cell source for regenerative therapies, but it is difficult to expand them in vitro without losing stemness. Standard culture on supraphysiologically stiff tissue culture plastic activates mechanosensitive signaling linked to osteogenic differentiation and reduced multipotency. Although very soft materials (∼1 kPa) are known to preserve stemness, proliferation decreases in a stiffness-dependent manner, and hydrogels in the 5-30 kPa range promote early osteogenic signaling and loss of stemness through integrin-driven mechanotransduction. Here, we use norbornene-modified hyaluronic acid hydrogels to tune substrate stiffness and peptide presentation for the culture of human MSCs. Increasing RGD concentration on 5-20 kPa hydrogels elevates cell spreading and nuclear localization of the mechanosensitive regulator Yes-associated protein (YAP), demonstrating increased mechanosensing within this physiological stiffness range. Incorporation of the N-cadherin mimetic peptide HAVDI reduces cell spreading, increases circularity, and lowers nuclear YAP ratios within 24 h across these stiffness conditions, and decreases nuclear Runx2 levels over three days, indicating reduced activation of osteogenic-associated transcriptional signaling. Despite this reduced mechanosensing, MSCs proliferate similarly on HAVDI-containing and control hydrogels over two weeks, and cells expanded on HAVDI substrates exhibit improved retention of MSC surface marker profiles, including higher CD73 positivity and fewer cells expressing non-MSC-associated markers compared to tissue culture plastic. Together, these results identify a peptide-functionalized hydrogel platform that combines integrin and N-cadherin cues to modulate integrin-associated mechanosensing while supporting MSC expansion.

DOI: https://doi.org/10.1016/j.bioadv.2026.215102
Adv Mater. 2026 Aug 08. e74543

Flax Composites With Improved Interfacial Strength Through Microbially Induced Mineral Precipitation.

Deniz Sayinbas, Ingo Nettersheim, Jeong-Joo Oh, Marie-Eve Aubin-Tam, Julie Teuwen, Kunal Masania.

  Driven by the needs of modern transportation and the clean energy transition, the demand for sustainable and lightweight materials is increasing. Composite materials incorporating natural fibers such as flax fibers have gained attention due to their carbon-capturing potential and good specific mechanical properties. However, when embedded in hydrophobic polymer matrices, flax fibers exhibit inferior mechanical performance primarily due to their hydrophilic composition and discontinuous fiber architecture. Biological materials such as nacre have developed useful strategies through mineralization to distribute localized stresses and develop extrinsic toughness that could inspire a solution to enhance stress transfer in natural fiber composites. Here, we report a biomineralization strategy to introduce an additional hierarchy to flax composites. By tuning salt concentrations in the process, we achieve controlled deposition of microbe-mediated mineral particles on flax yarns. With controlled biomineralization, we show that the minerals can enhance the compressive toughness by 178% and compressive strength by 30%. The findings highlight a novel bio-inspired pathway for tailoring composite performance through sustainable processing, offering a scalable and environmentally friendly approach to enhance natural fiber composites for structural applications.

Keywords:  biomineralization; bio‐composites; bio‐inspired materials; flax fiber composites; microbially induced calcite precipitation (MICP)

DOI:  https://doi.org/10.1002/adma.74543
Trends Biotechnol. 2026 Aug 11. pii: S0167-7799(26)00296-9. [Epub ahead of print]

Engineered probiotics block arsenite absorption in the gastrointestinal tract.

Nhu Nguyen, Miaomiao Wang, Sithembiso S Msibi, Vincenzo Kennedy, Fateme Esmailie, L Joseph Su, Lin Li, Clement T Y Chan.

  Chronic exposure to arsenite in food and water is a major global health concern, yet no practical strategies exist to prevent ingested arsenite from entering the body through the gastrointestinal tract. Here, we engineered Escherichia coli Nissle 1917 (EcN) to sense and sequester arsenite in situ, creating a probiotic-based approach to reduce host absorption of arsenite. The system involved an arsenite-responsive genetic toggle switch that activated chelator expression upon exposure; after arsenite was removed, it sustained output under biostatic conditions but shut off during active cell division. We also engineered a nontoxic, high-affinity arsenite-binding protein as the chelator. The resulting strain efficiently removed arsenite in vitro while maintaining robust growth. A mass-transfer model guided in vivo dosing, and mouse studies showed that engineered EcN reduced arsenite entry into the bloodstream and promoted its fecal elimination. These findings support the conclusion that this engineered probiotic approach is promising for addressing toxic pollutants in the diet.

Keywords:  biological metal chelators; dietary arsenite; engineered probiotics; microbial sense and response; synthetic biology

DOI:  https://doi.org/10.1016/j.tibtech.2026.07.017
Nat Biotechnol. 2026 Aug;44(8): 1280

Microbiomics.

DOI: https://doi.org/10.1038/s41587-026-03250-w
Proc Natl Acad Sci U S A. 2026 Aug 18. 123(33): e2619198123

Molecular assembly as a universal biosignature measurable by mass spectrometry.

Lindsay A Rutter, Abhishek Sharma, Ian Seet, David Obeh Alobo, An Goto, Leroy Cronin.

  Detecting life beyond Earth requires biosignatures that do not depend on the chemistry of known organisms. Molecular assembly (MA), derived from Assembly Theory, quantifies how difficult it is to build a molecule from basic building blocks, linking complexity directly to selection and evolution. Here, we show that MA can serve as a universal biosignature that is both interpretable and experimentally measurable. Unlike information-theoretic measures, MA can be inferred directly from mass spectrometry data without structural elucidation. We demonstrate this using a machine learning model trained on standardized single-stage (MS1) spectra, which predicts MA with three-fold lower error than baseline methods. Simulated multistage (MSn) data reveal that small instrumental variations can double prediction error, highlighting the importance of calibration. These findings establish molecular assembly as a physically grounded, quantifiable biosignature measurable by mass spectrometry whose interpretation depends on careful control of instrumental effects, offering a scalable route to life detection on future planetary missions.

Keywords:  assembly theory; astrobiology; complexity; machine learning

DOI:  https://doi.org/10.1073/pnas.2619198123
J Am Chem Soc. 2026 Aug 12. 148(31): 33980-33989

Nanopore-Based Profiling of PEGylation in Nucleic Acid Therapeutics.

Gerardo Patiño Guillén, Thieme T Schmidt, Jeremy J Baumberg, Jack W Szostak, Ulrich F Keyser, Filip Bošković.

Nucleic acid therapeutics (NATs), including aptamers, offer effective strategies for programmable and targeted disease treatment. To improve their stability and circulation time, oligonucleotides are often conjugated to hydrophilic polymers, such as polyethylene glycol (PEG). However, current bulk techniques fail to resolve PEG heterogeneity, especially in complex biological environments. Here, we use nanopore sensing to quantify the PEG conjugation efficiency of the FDA-approved RNA aptamer pegaptanib. We assembled DNA nanostructures that bind pegaptanib, and then we used solid-state nanopores to quantify pegaptanib PEGylation. We further assessed pegaptanib PEGylation and stability in a serum background and demonstrated that nanopore sensing resolves PEG moieties of distinct molecular weights within the oligonucleotide conjugates. Single-molecule profiling of polymer-RNA conjugates enables iterative improvements in oligonucleotide design and provides a direct means to assess their stability in complex biological environments, thereby advancing the development of more effective NATs.

DOI: https://doi.org/10.1021/jacs.6c12398
Biofabrication. 2026 Aug 11.

Sequential stenciling to reconstitute 2D microtissues for multicellular and synthetic signaling architectures.

Kai Hirzel, Jasmin Čić, Stella Asmanidou, Nadja Schmohl, Roland E Kontermann, Satoshi Toda, Monilola A Olayioye, Andrew G Clark, Michael Heymann.

  In mammalian organisms, native tissue function depends on precise spatial organization down to the cellular level. Reconstituting tissue architectures in 2Din vitroplatforms can provide a means to study direct and indirect cell-cell interactions in a variety of tissue contexts while remaining compatible with high-throughput assays and high-resolution live imaging. We combine cost-effective stereolithography leveraging 3D printing with replica molding to stencil spatially defined, multicellular culture systems with sub-millimeter resolution onto planar substrates. The system is designed for ease of use, requires no complex fabrication setups and scales readily to 96-well plates. Sequential stencil application and removal under a biosafety cabinet enables controlled positioning of multiple cell types and supports the maturation of tissue assemblies. We demonstrate the utility of this stencil-based patterning strategy in three applications. First, we employ a combination of two circular stencils to recreate a structural feature characteristic of the tumor microenvironment of solid tumors: the encapsulation of colorectal cancer cells by cancer-associated fibroblast cells. Resulting cell patternings recapitulate key aspects of native tissue dynamics of the densely packed tumor tissues, in which cancer-associated fibroblast cells actively compress the cancer cells and confer targeted therapy resistance. Second, we probe an engineered synNotch-based signaling system in patterned cell patches that mimics morphogen gradient formation, where GFP-secreting sender cells generate a ligand-dependent gradient. Third, we recapitulate the characteristic crypt-villus architecture of the mammalian intestine by patterning intestinal organoids within a stencil-restricted crypt region and allowing differentiating cells to collectively migrate along a designed villus axis. The presented strategy allows for rebuilding multicellular tissue architecturesin vitrowith biologically relevant spatial precision for high-throughput drug screenings and dissection of tissue-specific cellular interactions.

Keywords:  co-culture; intestinal homeostasis; micropatterning; microtissue; synthetic morphogenesis; tumor microenvironment

DOI:  https://doi.org/10.1088/1758-5090/ae9807
Nat Methods. 2026 Aug 11.

Decoding mechanoregulation in immunological synapses using biomimetic artificial cells.

Xiaolei Yu, Vincent Mukwaya, Minxing Yue, Shuo Yang, Qian Li, Weili Zhao, Chunhai Fan, Lin Wang, Yingxi Zhao, Hongkai Yang, Jiacan Su, Li Wang, Hongjing Dou.

Mechanical force-driven signaling has emerged as a key regulator of cell-cell interactions (CCIs), which can enhance immune cell function. However, current biochemical approaches for studying CCIs offer minimal direct control over cellular bulk phenotypes, while synthetic biomaterial systems fail to mimic the dynamic complexity of cells. Here we introduce kpiCells, a biomaterial-based platform that uses a biomimetic membrane-endoplasmic architecture to enable finely tuned phenocopying of cellular states via modular mechanical, chemical and topographical inputs. We demonstrate that kpiCells can engage in physiological CCIs and reproduce critical subcellular features. In T cell systems, kpiCells enable integrated interrogation of afferent mechanosensing pathways and efferent force-exertion pathways, and support measurement of piconewton-scale forces at individual T cell antigen receptors as well as single cell-cell force fingerprints that define activation thresholds. This work establishes kpiCells as a bionic model that enables synthetic material design with the level of functional complexity approaching living cell systems.

DOI: https://doi.org/10.1038/s41592-026-03199-3
ACS Appl Mater Interfaces. 2026 Aug 12. 18(31): 43309-43320

Versatile Compartmentalization of Hydrogel-Medium Interfaces in Microfluidic Channels for Reconstructing Complex Tissue Architectures.

Byengkyu Kang, Yong Hun Jung, Ju-Hee Kim, Dong-Hee Choi, Jaehoon Kim, Kyungwon Park, Minseop Kim, Seok-Hyeon Kang, Kyuhwan Na, Sejoong Kim, Hyung Chul Kim, Hyunho Kim, Minsuh Kim, Seok Chung.

  Replicating in vivo tissues with complex, branched, and tortuous geometries remains a challenge in engineering physiologically relevant tissue models. Hydrogel compartmentalization in microfluidic chips can spatially organize cells and microenvironments, but micropillar-based confinement relies on discrete structures that generate segmented interfaces and can limit the design of continuous, nonlinear compartment boundaries. Here, we develop a weir-based microfluidic platform that forms continuous hydrogel-medium boundaries and enables stable hydrogel patterning across diverse, tissue-relevant architectures. We establish a predictive, pressure-based design framework that relates geometric parameters to the minimum pressure required to advance the gel front and the maximum pressure tolerated before interface failure. Using theoretical analysis and computational simulations, we identify intersection geometries that are susceptible to failure and provide practical layout guidelines to improve filling stability in complex networks. We validate these predictions experimentally and demonstrate reliable compartmentalization across extended branched networks, interwoven gel-medium channel architectures, and multihydrogel designs. Finally, we demonstrate biological applicability by engineering complex interconnected 3D vascular networks and continuous renal epithelial tubes that conform to complex and curved microchannels and by quantifying how local connectivity and spatial architecture drive region-specific tissue morphogenesis. Together, these results improve the predictability and expand the design versatility of weir-based microfluidic platforms for hydrogel compartmentalization in complex geometries.

Keywords:  compartmentalization; hydrogel; microfluidic chips; pressure framework; weir-based design

DOI:  https://doi.org/10.1021/acsami.6c07941
Curr Opin Biotechnol. 2026 Aug 13. pii: S0958-1669(26)00132-1. [Epub ahead of print]101 103567

Yeast single-cell proteins from CO2 with tandem biological systems.

Cheng-Cheng Ding, Pei-Ru Chen, Shu-Guang Wang, Peng-Fei Xia.

Production of customized yeast single-cell protein (SCP) from CO2 offers a sustainable avenue to convert a major carbon emission process into a carbon-conserving production route of food and feed. Here, we highlight a specific approach for SCP production from CO2 using sequentially connected yet spatially separated tandem biological systems, which consist of a first unit for CO2 fixation followed by a second unit for precision fermentation toward customized SCPs. We discuss the design principles of the system, review current efforts to convert CO2 using natural and engineered autotrophs, and outline the potential of yeast for customized SCP production. Finally, we underscore the critical role of nitrogen sources for efficient SCP production.

DOI: https://doi.org/10.1016/j.copbio.2026.103567
Mater Horiz. 2026 Aug 12.

3D printable tough hydrogel actuators.

Allison L Chau, Esther Amstad.

Nature autonomously actuates many of its structures in response to changes in environmental conditions. Inspired by nature, stimuli-responsive hydrogel-based actuators that wirelessly operate without external energy sources have been developed. By exploiting the tunable swelling behavior of hydrogels, these systems can actuate in the form of bending, twisting, folding, and even locomotion. However, for these materials to function effectively across a broad range of applications, their mechanical properties - especially their stiffness and toughness - must be improved to increase their actuation force and operational reliability. Addressing these mechanical performance challenges in hydrogel-based actuators would bring them closer to replicating the remarkable combination of mechanical toughness, resilience, and actuation observed in nature. This review outlines established toughening strategies for hydrogels and highlights advances in their additive manufacturing into actuators with well-defined structures and locally varying compositions. It concludes with a brief outlook on potential opportunities that arise if self-healing or improved fatigue resistance are incorporated into actuating systems.

DOI: https://doi.org/10.1039/d6mh00947f
Nature. 2026 Aug 12.

Structural mechanism governing the directionality of bridge recombination.

Masahiro Hiraizumi, Januka S Athukoralage, Nicholas T Perry, Eisuke Tsujimoto, Nami Shiojiri, Naoto Nagahata, Lauren Lee, Gwanggyu Sun, Matthew G Durrant, Sita S Chandrasekaran, Silvana Konermann, Keitaro Yamashita, Patrick D Hsu, Hiroshi Nishimasu.

Bridge recombinases from the IS110 family of transposons, such as IS621, associate with a bridge RNA (bRNA) to mediate programmable recombination between donor DNA and target DNA1,2. Although insertion is mediated by the recombinase-bRNA complex, it remains unknown how IS621 elements are excised from host genomes to form the circular DNA intermediates required for transposition. Here we show that bRNA is weakly expressed from IS621 loci in the Escherichia coli genome and that the IS621 recombinase-bRNA complex mediates excision less efficiently than insertion. Furthermore, we present the cryo-electron microscopy structures of the IS621 recombinase-bRNA complex bound to excision DNA substrates, providing mechanistic insights into the excision reaction. Similar to the previously reported donor- and target-bound insertion complex2, the excision complex comprises two recombinase dimers, each accommodating the target- and donor-binding loops of the bRNA. However, DNA recognition differs notably between the two complexes. Although the donor and target DNAs form a bent U-shape during insertion2, the excision substrates adopt linear conformations and bind across both bRNA loops, forming an X-shaped structure. This geometry reduces the efficiency of top-strand exchange and contributes to the naturally observed bias favouring insertion over excision. Despite these differences, the efficiencies of both reactions are similarly modulated by base pairing between specific dinucleotides in the bRNA, termed handshake guides, and the top strands of the DNA substrates. Overall, this study provides mechanistic insights into the complete IS110 transposition cycle and facilitates the optimal design of programmable bridge-editing applications.

DOI: https://doi.org/10.1038/s41586-026-10903-y
Proc Natl Acad Sci U S A. 2026 08 18. 123(33): e2609531123

The history of enzyme evolution embedded in metabolism.

Tatsuya Corlett, Harrison B Smith, Eric Smith, Joshua E Goldford, Liam M Longo.

  Whereas phylogenetic reconstructions are a primary record of protein evolution, it is unknown whether the deep history of enzymes is encoded at higher levels of biological organization. Here, we demonstrate that the emergence and reuse history of enzymatic folds is embedded within the web of metabolite-cofactor-enzyme interdependencies that comprise biosphere-scale metabolic reaction networks. Using a simple network analysis approach, we reconstruct the relative ordering of enzymatic fold emergence and, where possible, the first reaction(s) that each enzymatic fold catalyzed. We find that a large majority of enzymatic folds were sufficient as independent additions to open new avenues for metabolic growth. The resulting network-based histories are broadly concordant with enzyme phyletic distribution in prokaryotes, a proxy for enzyme age. Our results suggest that the earliest enzyme-mediated metabolisms were enriched for α/β proteins, likely due to their strong association with cofactor utilization, and that α-proteins preferentially emerge at later stages. The cradle-loop barrel, a member of the small β-barrel metafold, is predicted to be the founding β-fold, in agreement with analyses of ribosome structure. An examination of how the protein universe responded to the biological production of molecular oxygen reveals that the adaptation of existing enzymatic folds, not novel fold emergence, was the primary driver of metabolic evolution. This work presents a self-consistent model of metabolic and enzyme evolution, key progress toward integrating diverse perspectives into a unified history of protein evolution.

Keywords:  ECOD; KEGG; metabolism; network expansion; protein evolution

DOI:  https://doi.org/10.1073/pnas.2609531123
Sci Adv. 2026 Aug 14. 12(33): eaec3536

Single-exposure holographic 3D printing via inverse-designed phase masks.

Dajun Lin, Xiaofeng Chen, Connor J O'Dea, Ji-Won Kim, Keldy S Mason, Barbara Groh, Kwong Sang Lee, Apratim Majumder, Chih-Hao Chang, Michael Cullinan, Zachariah A Page, Rajesh Menon.

Additive manufacturing using light is commonly constrained by serial voxel-by-voxel or layer-by-layer processing, which fundamentally limits fabrication speed and scalability. Here, we introduce a single-exposure holographic three-dimensional (3D) printing approach that synthesizes an entire volumetric dose distribution optically in one step. The method combines inverse-designed microstructured phase masks with photopolymer resins engineered for controlled optical absorption. By precisely tailoring the phase-mask topography, we generate arbitrary 3D light-intensity distributions within the resin, including intentionally encoded dark regions that define hollow internal features. Simultaneously, the resin formulation is designed to balance optical penetration with sufficient local energy deposition to achieve high-fidelity polymerization throughout the volume. Using this approach, millimeter-scale architectures comprising more than 106 addressable voxels are fabricated in a single 7.5-second exposure, corresponding to a volumetric throughput of ∼1 cubic millimeters per second (>105 voxels per second). The demonstrated performance is presently limited by resin kinetics and illumination geometry rather than by the phase-mask framework itself. Because the volumetric information capacity scales with the space-bandwidth product of the phase mask, this approach provides a clear pathway toward substantially higher throughput, enabling scalable fabrication of micro-optical components, biomedical scaffolds, and other precision-engineered mesoscale systems.

DOI: https://doi.org/10.1126/sciadv.aec3536
Trends Biotechnol. 2026 Aug 04. pii: S0167-7799(26)00291-X. [Epub ahead of print]

Conductive and magnetic silk biomaterials: functionalization strategies and challenges for sustainable bioelectronics.

Gabriele Greco, Ferdinando Auricchio, Michele Conti, Vamsi K Yadavalli.

  Silk protein-based biomaterials are attractive because of their mechanical performance, biocompatibility, and processability into fibers, films, and hydrogels. Recent efforts have focused on integrating electrical conductivity and magnetic responsiveness for bioelectronics, biosensing, neural interfaces, and regenerative medicine. This review examines how these functionalities can be incorporated into natural and recombinant silk materials through pre- and post-assembly strategies across different material formats. Particular attention is given to their effects on protein structure, long-term stability, biocompatibility, and environmental sustainability. By identifying the trade-offs between functionality and material integrity, this review outlines design principles and future directions for developing sustainable silk-based bioelectronic materials.

Keywords:  biosensors; composites; life cycle assessment; nanomaterials; nature-derived; sustainability

DOI:  https://doi.org/10.1016/j.tibtech.2026.07.012
Cell. 2026 Aug 14. pii: S0092-8674(26)00872-X. [Epub ahead of print]

Polyamines buffer labile iron to suppress ferroptosis.

Pushkal Sharma, Heather R Keys, Ryan P Mansell, Jillian Stark, Louisa Girard, Christalyn Ausler, Rachel Anderson, Sebastian Müller, Shinya Imada, Ivan S Pires, Tenzin Kunchok, Millenia Waite, Bingbing Yuan, Amy Deik, Luke Ferro, Paula T Hammond, Raphaël Rodriguez, Maria-Eirini Pandelia, Whitney S Henry, Ankur Jain.

  Polyamines are essential and evolutionarily conserved metabolites present at millimolar concentrations in mammalian cells. Cells tightly regulate polyamine homeostasis through complex feedback mechanisms, yet the precise role necessitating this regulation remains unclear. Here, we show that polyamines contribute to endogenous buffering of redox-active iron, providing a molecular link between polyamine metabolism and ferroptosis. Using a genome-wide CRISPR screen, we identified a synthetic lethal dependency between polyamine depletion and the key ferroptosis suppressor, glutathione peroxidase 4 (GPX4). Mechanistically, we show that polyamine deficiency triggers a redistribution of cellular iron, increasing the labile iron pool and upregulating ferritin. To directly visualize this iron buffering in living cells, we developed a genetically encoded fluorescent reporter for redox-active iron. Live-cell analysis revealed a striking inverse correlation between intracellular polyamine levels and redox-active iron at single-cell resolution. These findings reposition polyamines as key regulators of iron homeostasis, with implications for ferroptosis-linked disease states and cellular redox balance.

Keywords:  GPX4; ferroptosis; genetically encoded iron sensor; iron homeostasis; labile iron pool; polyamines; redox-active iron; spermidine; spermine

DOI:  https://doi.org/10.1016/j.cell.2026.07.040
Nat Plants. 2026 Aug 14.

Bottom-up reconstruction of synthetic pyrenoids provides insights into the mechanisms and evolution of carbon concentration by EPYC1 proteins.

A M Küffner, B Pommerenke, L Kley, J Z Y Ng, S Prinz, M Tinzl-Zechner, L Schulz, P Claus, N Paczia, T Chotel, M Klose, J Zarzycki, G K A Hochberg, T J Erb.

Membraneless organelles play essential roles in many cellular processes. In various photosynthetic organisms, they are a crucial part of CO2/carbon-concentrating mechanisms (CCMs) that increase photosynthetic productivity. One example is the pyrenoid in Chlamydomonas reinhardtii, a liquid-phase-separated organelle that localizes and improves CO2 fixation via the intrinsically disordered protein essential pyrenoid component 1 (EPYC1CR). Modern-day pyrenoids are complex structures with an elaborate cellular architecture and dozens of components, raising the question of how they could have developed from simpler condensates. Here we develop a bottom-up approach to study the function of EPYC1s and explore their sequence-function space across phylogenetic diversity and evolution. We demonstrate that extant and ancestral EPYC1 sequences induce phase separation of Rubisco into synthetic pyrenoids with functional CCMs. Surprisingly, these CCMs are mainly based on enhanced carboxylation rates (rather than increased specificity), offering new insights into the construction, function and evolution of natural and synthetic pyrenoids.

DOI: https://doi.org/10.1038/s41477-026-02349-x
ACS Appl Bio Mater. 2026 Aug 10.

Metal Ion-Triggered Collapsed Hydrogels as Materials for Bacterial Population Control.

Danniel Gee, Roser Montagud-Martínez, Rosa Adam, Carlos J Gómez-García, Guillermo Rodrigo, Rafael Ballesteros-Garrido.

  Hydrogels are versatile soft materials extensively employed in applications ranging from biomedicine to environmental technologies owing to their high water content and tunable physicochemical properties. In this work, we describe a metal ion-induced collapse phenomenon in poly(vinyl alcohol) (PVA)-borate hydrogels triggered by Cu2+ cations, leading to a class of materials termed metal ion-triggered collapsed hydrogels (MitCH). Upon increasing the concentration of copper sulfate, conventional PVA-borate hydrogels undergo an abrupt contraction accompanied by water expulsion and formation of a rubbery, mechanically robust solid enriched in copper and boron species. Elemental and ICP analyses reveal copper loadings of up to ∼14 % wt, whereas sulfate and sodium ions are largely released during collapse, indicating extensive reorganization of the coordination environment. The collapse process occurs at neutral pH and depends critically on copper concentration, counterion identity, and the molecular weight and degree of hydrolysis of PVA. Structural characterization suggests non-crystalline structures; however, electron paramagnetic resonance clearly evidences antiferromagnetically coupled copper centers. MitCH materials remain stable in water but dissolve in nutrient-rich biological media, enabling environmentally responsive release of copper ions. This behavior was successfully exploited to control the growth of Escherichia coli, showing complete inhibition at sufficient material loadings. These findings demonstrate that MitCH materials constitute a promising platform for controlled antimicrobial applications combining simple water-based preparation methodology, relatively high metal loading, aqueous stability, and environment-responsive release.

Keywords:  bacterial control; collapsed hydrogels; controlled release; copper-containing materials; hydrogels

DOI:  https://doi.org/10.1021/acsabm.6c00678
J Biol Chem. 2026 Aug 04. pii: S0021-9258(26)02256-8. [Epub ahead of print] 113384

A modular platform for measuring substrate oxidation by CO2 production in diverse cell culture systems.

James R Krycer, Shubhangi Seth, Lynn A C Devilée, Mary Lor, Rebecca L Fitzsimmons, Richard J Mills, Yan Lu, Prarthna G Bhaskaran, Mark Hodson, James E Hudson, Severine Navarro.

Metabolism underpins cellular physiology, whereby the preference for specific substrates and catabolic pathways shapes the production of energy, anabolic substrates, and metabolite signals to address bioenergetic demands. Substrate catabolism can be directly examined by measuring metabolic endpoints. For instance, substrate oxidation can be quantified by the incorporation of carbon from labelled glucose or fatty acids into carbon dioxide, providing a sensitive and specific readout of metabolic flux. However, current platforms require relatively large culture volumes, lacking adaptability for small-scale or complex cell culture formats. Herein, we develop and validate a modular platform that can quantify substrate oxidation in a range of cell culture systems, including two- and three-dimensional cultures grown in 12- and 96-well plate formats. This platform was engineered for precise gas equilibration, minimal gas leakage, and bioinert adapters suitable for smaller-scale cultures, using inexpensive and accessible components. We demonstrate the versatility of this system by showing that: (i) dendritic cells modulate glucose catabolism in response to a tolerance-inducing biologic (AIP-2), and (ii) human cardiac organoids maintain fatty acid oxidation during acute inflammatory stress. This platform can be performed in parallel with orthogonal metabolomics assays and live-cell imaging, enabling integrated analysis of metabolic and functional readouts. Together, this platform expands access to measuring substrate oxidation across a range of cellular systems.

DOI: https://doi.org/10.1016/j.jbc.2026.113384