bims-enlima 2026-05-03 papers

bims-enlima

Biomed News

on Engineered living materials

Issue of 2026–05–03
24 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool

Fiber-Based Hydrogels for Designing Viscoelastic Responses in Particle-Based Biomaterials That Support Embedded 3D Printing.
Selective Covalent Assembly of Gram-Negative Bacteria and Synthetic Polymers into Functional Living Materials.
Biosynthesized Silk-Amyloid-Mussel Proteins as Dissolution Recyclable Materials With Tunable Supercontraction.
Switchable DNA-Scaffolded Multivalent Aptamer through Stimuli-Responsive Plug-and-Play Modules for Protein Regulation.
Physiological Buffer Selection Alters the Mechanics of Hydrogels with Hydrazone Cross-Links.
Toward life with a 19-amino acid alphabet through generative artificial intelligence design.
The past, present and future of de novo protein design.
Programmable ion-protein networks from sodium caseinate: a sustainable platform for soft functional materials.
Mechanically Induced Adaptive Self-Growing Protein Hydrogel.
Programmable artificial RNA condensates in mammalian cells.
Viscoelasticity of the Heart: An Overview of Viscoelastic Measurements at Different Scales.
Engineered conductive pili enable high-efficiency photosynthetic electron extraction in biophotovoltaics.
Gene syntax defines supercoiling-mediated transcriptional feedback.
3D-Printed, Ultrastretchable Polychloroprene Elastomers via Thiol-ene Photopolymerization.
PALINCODE: Recording cell lineage with ternary palindromic CRISPR bits.
An exceptionally conductive hydrogel for all-organic, ultraflexible, and chronic neural interfaces.
Engineered Channel Asymmetry Extends Hydrogen-Bonding Networks for Proton Conduction.
STRAIGHT-IN Dual: a platform for dual single-copy integrations of DNA payloads and gene circuits into human induced pluripotent stem cells.
Enhanced electrochemical and thermoelectric performance of bacterial cellulose-based composite aerogels via multi-component reinforcement.
Soft, Skin-Conformal Electronic Interfaces for Multimodal Biosignal Monitoring and Transcutaneous Stimulation.
Lifetime-based multiplexed detection of viral RNA using fluorogenic aptamers.
Wood that bonds itself via homologous adhesion through cellulose reconstitution.
One-pot expression of an oligoclonal nanobody-based antivenom in growth-decoupled Escherichia coli.
Fibrillar adhesion dynamics govern the timescales of nuclear mechano-response via the vimentin cytoskeleton.

ACS Biomater Sci Eng. 2026 May 01.

Fiber-Based Hydrogels for Designing Viscoelastic Responses in Particle-Based Biomaterials That Support Embedded 3D Printing.

M Gregory Grewal, Emily Ferrarese, Lauren Porter, Georgia T Helein, Christopher B Highley.

  Viscoelastic biomaterials that exhibit biomimetic responses to applied stresses are important in studying physiology and designing biomaterial scaffolds. Particle-based hydrogels offer potential for engineering viscoelasticity through the design of both the component microparticles and their processing into bulk particle-based materials. When particles are not cross-linked to one another, particle movements in response to strain can potentially relieve applied stresses and facilitate the material's use in dynamic processes like bioprinting. In particle-based hydrogels based on spherical hydrogel microparticles (HMPs), particle movement is restricted by contact with immediately adjacent HMPs. In comparison, fiber-based hydrogel systems leverage high-aspect-ratio microfiber components with long-range interactions. Here, microfibers with aspect ratios of ∼15:1 length/diameter are used to form particle-based hydrogels to compare how interparticle interactions at increased length scales alter properties compared to particle-based hydrogels based on spherical HMPs. Like particle-based hydrogels formed from spherical HMPs, those formed from fiber HMPs exhibit viscoelasticity with shear-thinning and self-healing behaviors. But fiber-based materials allow enhanced control over bulk stress relaxation times (T1/2 ∼ 1-100+ s) across a range of applied strains (σ ∼ 2.5%-50%) in a packing density-dependent fashion. Fiber-based systems relaxed stresses continuously and to a greater degree at low strains in comparison to HMP systems. Dynamic interfiber interactions in fiber-based hydrogels also supported embedded printing, where perfusable channels can be printed into fiber-based hydrogels stabilized by physical interfiber interactions. Taken together, fiber-based hydrogels offer opportunities for designing complex biomaterial scaffolds, including allowing control over viscoelastic properties through hydrogel design and control over heterogeneous 3D structures through embedded printing.

Keywords:  dynamic materials; embedded printing; granular hydrogels; microfibers; particle-based hydrogels; stress relaxation

DOI:  https://doi.org/10.1021/acsbiomaterials.5c01432
J Am Chem Soc. 2026 Apr 27.

Selective Covalent Assembly of Gram-Negative Bacteria and Synthetic Polymers into Functional Living Materials.

Omkar Mohapatra, Yuwen Wang, Minh-Anh Dinh, Han Li, Maria Rebolleda-Gomez, Seunghyun Sim.

Here, we report selective covalent assembly of Gram-negative bacteria and synthetic polymers into functional living materials. We discovered that triblock polymers decorated with vinyl sulfone (VS), a motif that forms a stable covalent bond with cysteine residues on surface proteins, yielded stable covalent assembly with bacterial cells. Notably, we found that these assemblies were uniquely cell-type-specific, occurring only in Gram-negative bacteria, highlighting differences in surface structures and the macromolecular diffusion barrier across bacterial species. We also demonstrated that assembling engineered cells into materials results in situ melanin production from living materials, with robust biocontainment and mechanical reinforcement. Spontaneous enrichment of tyrosine-derived red pigments in the supernatant showcases the effect of confinement in a complex biochemical pathway. This work establishes a platform for encoding complex, engineered, and evolved functions of Gram-negative bacteria into synthetic materials, enabling the development of a wide range of material-based bioreactors.

DOI: https://doi.org/10.1021/jacs.6c04104
Adv Mater. 2026 Apr 29. e73200

Biosynthesized Silk-Amyloid-Mussel Proteins as Dissolution Recyclable Materials With Tunable Supercontraction.

Jingyao Li, Juya Jeon, Kok Zhi Lee, Fuzhong Zhang.

Dissolution recycling represents a promising and potentially cost-effective strategy for material regeneration and greenhouse gas reduction. Yet, very few polymers are practically recyclable by dissolution because strong intermolecular interactions, essential for mechanical performance, are typically incompatible with solvent disruption during dissolution. Here, we present a rational material engineering approach that balances these competing requirements to create high-performance, dissolution-recyclable protein-based materials (PBMs). Using protein engineering and synthetic biology, we designed silk-amyloid-mussel (SAM) protein hybrids whose amorphous domains control solvent ingress, while crystalline domains maintain load-bearing intermolecular interactions. The engineered SAM fibers, SAMHY, exhibited exceptional tensile strength (401 ± 40 MPa), toughness (124 ± 38 MJ/m-3), and minimal supercontraction (2.2% ± 1.9%) under high humidity (>90%), alongside full recyclability through a rapid (<1 h), energy-efficient dissolution process using aqueous formic acid. Recycled fibers retained both structural integrity and mechanical performance over multiple recycling cycles. Moreover, the recycled SAMHY protein was reprocessed into hydrogels with strong underwater adhesion and mechanical robustness even after further recycling. These findings establish fundamental design principles for recyclable PBMs and demonstrate the feasibility of producing versatile, high-performance, sustainable, and recyclable protein materials for a broad range of applications.

DOI: https://doi.org/10.1002/adma.73200
ACS Appl Mater Interfaces. 2026 Apr 30.

Switchable DNA-Scaffolded Multivalent Aptamer through Stimuli-Responsive Plug-and-Play Modules for Protein Regulation.

Kaiqi Xu, Ji Zhao, Guang Hu, Liming Shao, Jie Song, Linlin Tang.

  Multivalent molecular interactions enhance binding affinity and enable functional regulation in biological systems, inspiring the development of multivalent materials for biosensing and biomedical applications. The capacity to reversibly switch between low-valency and multivalency as needed is key to regulating their function. However, current design strategies face challenges in enabling such switching within the same system through a response to multiple stimuli. Here, as a proof of concept, we demonstrate a switchable multivalent system for regulating thrombin activity. This system is based on thrombin aptamer-decorated DNA tile assembly and introduces stimuli-responsive plug-and-play modules that serve as dynamic, reversible, and orthogonal switches responding to the corresponding stimuli, including UV light, APE1, and RNase H. We construct three-layer switching cascades activated by one-, two-, or three stimuli to regulate thrombin activity. Building upon this programmable multivalent aptamer system, we further translate switchable modules into spatiotemporal control logic to construct a tristate circuit. We hope that the switchable DNA scaffold-based multivalent regulatory approach can provide a versatile modular platform with potential applications in precision medicine, biosensing, and biomaterials.

Keywords:  DNA self-assembly; Multivalent aptamer; Plug-and-play modules; Protein regulation; Stimuli-responsive switches

DOI:  https://doi.org/10.1021/acsami.6c02130
Biomacromolecules. 2026 Apr 28.

Physiological Buffer Selection Alters the Mechanics of Hydrogels with Hydrazone Cross-Links.

Daiyao Zhang, Neil J Baugh, Narelli de Paiva Narciso, Sarah C Heilshorn.

Hydrogels are used for a wide range of biomedical applications. While mechanical characterization of hydrogels is frequently performed in isotonic saline, the chemical identity of these solutions may vary widely from the ionic environments encountered during their use. To explore this idea, we test the mechanical properties of a hydrogel cross-linked with dynamic covalent chemistry (DCC) in several physiologically relevant ionic solutions that mimic different biological conditions. Specifically, we evaluate rheological properties of a hydrazone-cross-linked hydrogel composed of recombinant, chemically modified hyaluronan and elastin-like protein (ELP). Our results show that the shear moduli and stress relaxation properties of DCC hydrogels can vary significantly in different ionic environments. We identify the thermoresponsive nature of ELP and changes in hydrazone bond kinetics as the primary reasons for the observed differences in mechanical properties. Taken together, this work elucidates mechanisms underpinning changes in hydrogel mechanics in different physiological solutions.

DOI: https://doi.org/10.1021/acs.biomac.5c02684
Science. 2026 Apr 30. 392(6797): eaeb5171

Toward life with a 19-amino acid alphabet through generative artificial intelligence design.

Liyuan Liu, Charlotte Rochereau, Simon Kozlov, Guillaume Urtecho, Xiaonan Liu, Jiahui Zhao, Jasmine Wang, Yiming Huang, Yiming Qu, Zetian Zhang, Tomasz Blazejewski, Avi Swartz, Sergey Ovchinnikov, Harris H Wang.

Because all known living organisms are made from at least 20 canonical amino acids, the feasibility of life using a more simplified alphabet remains unclear. In this work, we leveraged computational design and synthetic biology to explore building a cell from a 19-amino acid alphabet. Initial analyses suggested that isoleucine (Ile) may be dispensable, which we confirmed by directly replacing Ile residues in essential proteins in Escherichia coli. Critically, protein language models and structure-based models were necessary to redesign functional Ile-less proteins in most cases. We systematically replaced all 382 Ile residues from the ribosome and combined 21 redesigned subunits at a native genomic locus to produce a viable, evolutionarily stable cell. This work provides a roadmap to create the first 19-amino acid organism since early evolution.

DOI: https://doi.org/10.1126/science.aeb5171
Nature. 2026 Apr;652(8112): 1139-1152

The past, present and future of de novo protein design.

Wei Yang, Shunzhi Wang, Gyu Rie Lee, Jason Z Zhang, Alexis Courbet, David Juergens, Xinru Wang, Thomas Schlichthaerle, Mohamad Abedi, Robert Ragotte, Linna An, Indrek Kalvet, Sam Pellock, Ljubica Mihaljevic, Cameron Glasscock, Arvind Pillai, Adam Broerman, Nathan Ennist, Ella Haefner, Nora McNamara-Bordewick, Ian Haydon, Lance Stewart, Gaurav Bhardwaj, David Baker.

With deep-learning-powered advances in protein design methods, there is an ongoing paradigm shift in protein engineering from random selection to intentional computational design methods. Here we describe the current state of de novo protein design. While there is still room for improvement in success rates and activities, the long-standing challenges of designing new protein structures, assemblies and protein binders are close to being solved. The key current questions in these areas are not how to design, but what to design, and open-source design methodology such as RFdiffusion and ProteinMPNN together with protein structure prediction tools enable biochemists and molecular biologists to broadly explore possible applications. There has also been considerable progress in the de novo design of small-molecule target binders, enzymes and multistate protein systems. Current challenges for methods development include design of catalysts for reactions with high energy barriers and, more generally, design of switches and nanomachines that integrate binding, conformational change and catalysis. Over the next five to ten years, we anticipate the design of sophisticated protein nanomachines and materials with functionality ranging far beyond that generated during natural evolution for a wide range of applications in medicine, technology and sustainability.

DOI: https://doi.org/10.1038/s41586-026-10328-7
Mater Horiz. 2026 Apr 29.

Programmable ion-protein networks from sodium caseinate: a sustainable platform for soft functional materials.

Pietro Tordi, Verónica Montes-García, Virginia Losasso, Artur Ciesielski, Paolo Samorì, Massimo Bonini.

Ion-protein coordination represents an underexploited design principle to assemble multiresponsive, soft, sustainable materials. Here, we harness sodium caseinate to construct programmable ionically crosslinked hydrogels in which multivalent cation selection governs the network architecture and enables a broad tunability of mechanical and other functional properties. A systematic study of cation types, including Ca2+, Sr2+, Ba2+, Mn2+, Cu2+, Zn2+, Fe3+, Al3+, and Zr4+, revealed pronounced ion-specific control over mechanical stiffness (1.5 kPa to 1.8 MPa), thermal stability, and hierarchical architecture. Multimodal characterization of their compositional, structural, morphological, thermal, spectroscopic, and mechanical properties enabled the tailoring of an empirical packing hierarchy for MX+-caseinate networks (MCas). Leveraging this tunability, we demonstrate proof-of-concept piezoresistive soft sensors in which ionic crosslinking of caseinate modulates the mechanical properties of caseinate-gelatin organohydrogel matrices. These matrices, crosslinked with Sr2+ and Zn2+, exhibit linear ΔR/R0 responses with gauge factors (1.84-2.20) competitive with state-of-the-art organohydrogel sensors. Real-time measurements further demonstrate their ability to detect bending angles and encode dynamic inputs, such as Morse code signals. These results position MCas as a sustainable, ion-tunable platform for the rational design of mechanically programmable protein hydrogels, opening opportunities in bioinspired materials for soft electronics and wearable sensing.

DOI: https://doi.org/10.1039/d6mh00390g
Adv Mater. 2026 May 02. e23636

Mechanically Induced Adaptive Self-Growing Protein Hydrogel.

Tingting Ma, Wei Sun, Meng Qin, Shen Yin, Yiran Li, Yi Cao, Bin Xue, Wei Wang.

  Living tissues strengthen under repeated mechanical loading, yet replicating such adaptive growth in synthetic materials remains a formidable challenge. Here, we report a protein-based hydrogel that undergoes mechanochemically induced self-growth, autonomously reinforcing its baseline mechanical properties under applied stress. This strategy harnesses the copper-storage protein Csp1, whose force-regulated unfolding releases Cu(I) that catalyzes in situ azide-alkyne cycloaddition, generating secondary crosslinks under mechanical load. Upon unloading, Csp1 refolds and re-sequesters Cu(I), halting catalysis and restoring growth capacity. This mechano-catalytic feedback loop enables stress- and time-dependent self-reinforcement within a closed system, without external monomer supply. The hydrogel exhibits programmable mechanical memory via leveraging Cu(I) homeostasis in cyclic growth-pause-growth transitions. By coupling force-dependent protein conformational dynamics with catalytic activity, this strategy establishes a generalizable mechanochemical framework for designing self-adapting biomaterials whose structure and function evolve under mechanical stimulation.

Keywords:  mechano‐induced reaction; mechano‐responsive properties; protein hydrogels; self‐growing materials; single‐molecule force spectroscopy

DOI:  https://doi.org/10.1002/adma.202523636
Nat Nanotechnol. 2026 Apr 29.

Programmable artificial RNA condensates in mammalian cells.

Shiyi Li, Yuna Kim, Kevin Wang, Eric John Payson, Anli A Tang, Maria Villalba Nieto, Dino Osmanovic, Madison Yang, Diego Dilao, Alexandra Bermudez, Wen Xiao, Melody M H Li, Neil Y C Lin, Kathrin Plath, Douglas L Black, Elisa Franco.

Artificial biomolecular condensates have emerged as powerful tools for controlling cellular behaviour. Here we introduce a method to build artificial condensates within living mammalian cells by designing modular RNA motifs composed of a single short RNA strand. These condensates emerge spontaneously, creating RNA-rich compartments that remain separated from their surrounding environment. The RNA sequences include stem-loop domains that fold as the RNA is transcribed, and then condense in the nucleus and cytoplasm through loop-loop interactions. These sequences can be optimized and diversified, enabling the generation of distinct, non-mixing condensate populations and the programmable control of their subcellular localization. The RNA motifs can also be modified to recruit small molecules, proteins and RNA molecules in a sequence-specific manner to the RNA-rich phase. By introducing RNA linkers, we can build condensates with multiple subcompartments, whose organization can be controlled by tuning the linker stoichiometry. These artificial condensates provide a versatile platform for studying and manipulating molecular functions inside living cells.

DOI: https://doi.org/10.1038/s41565-026-02164-7
Annu Rev Biomed Eng. 2026 May;28(1): 53-78

Viscoelasticity of the Heart: An Overview of Viscoelastic Measurements at Different Scales.

Marissa Gionet-Gonzales, Gabriela Villalpando Torres, Ryan S Stowers, Beth L Pruitt.

  The heart is viscoelastic and exhibits both viscous and elastic behavior with deformation. Cardiac viscoelasticity influences heart function by regulating the volume of blood that can fill, and subsequently be pumped from, the cardiac chambers. Tissue viscoelasticity can also influence cellular functions, motivating the need to measure and model viscoelasticity from the cellular to the organ scale under healthy and disease conditions. Here, we review current protocols, instrumentation, and results from cardiac viscoelastic measurements from the organ to the subcellular level. Since viscoelasticity is regulated by tissue structure and composition, we describe what is known about the viscoelasticity of intracellular and extracellular proteins, cardiac cells, and cardiac tissue, as well as how changes in these proteins with disease progression may influence cardiac viscoelasticity. Finally, we discuss the outlook for the field, including recommendations for standardizing reports of cardiac viscoelastic measurements to increase their utility for biomaterials design for tissue engineering, cardiovascular modeling, and diagnosis.

Keywords:  biomechanics; cardiomyocyte; mechanical measurements; viscoelasticity

DOI:  https://doi.org/10.1146/annurev-bioeng-020625-023632
Nat Commun. 2026 Apr 25.

Engineered conductive pili enable high-efficiency photosynthetic electron extraction in biophotovoltaics.

Haowei Wang, Yanping Zhang, Yin Li, Huawei Zhu.

The efficient extraction of electrons from photosynthetic microorganisms remains a critical challenge in living biophotovoltaics (BPV). While nanomaterials can facilitate electron transport, their stochastic adsorption leads to inefficient material-wasteful interfaces. Here, we demonstrate a controllable approach to direct the targeted assembly of gold nanoparticles (AuNPs) onto the type IV pili of Synechocystis sp. PCC 6803 by using a genetically encoded gold-binding peptide. This approach creates a spatially precise conductive nano-bio interface on the cell envelope that serves as a dedicated electron conduit between photosynthetic electron transport chains (PETCs) and electrodes. This nano-bio interface enhances electron transfer through synergistic improvements in interfacial charge transfer and biofilm density, ultimately yielding a four-fold increase in photocurrent density, while using two orders of magnitude less gold than non-targeted strategies. Moreover, the AuNPs can be transferred from inactivated to fresh cells, indicating a potential pathway for long-term stability. This work establishes a generalizable strategy for the rational design of conductive interfaces on living cells, with implications for biophotovoltaics, microbial electrosynthesis, and next-generation biohybrid devices.

DOI: https://doi.org/10.1038/s41467-026-72407-7
Science. 2026 Apr 30. 392(6797): eadw1925

Gene syntax defines supercoiling-mediated transcriptional feedback.

Christopher P Johnstone, Kasey S Love, Sneha R Kabaria, Ross D Jones, Albert Blanch-Asensio, Deon S Ploessl, Emma L Peterman, Rachel Lee, Jiyoung Yun, Conrad G Oakes, Christine L Mummery, Richard P Davis, Brandon J DeKosky, Peter W Zandstra, Kate E Galloway.

Gene syntax-the order and arrangement of genes and their regulatory elements-shapes the dynamic coordination of both natural and synthetic gene circuits. Transcription at one locus perturbs the transcription of adjacent genes, but the molecular basis of this effect remains poorly understood. In this work, we show that supercoiling-mediated feedback arises from transcription and regulates expression of adjacent genes in a syntax-specific manner. Using a suite of assays, we measured syntax- and induction-dependent formation of chromatin structures in human induced pluripotent stem cells. Applying syntax as a design parameter, we built and improved compact gene circuits, tuning the expression mean, noise, and stoichiometry across delivery methods and cell types. Integrating supercoiling mediated feedback into models of gene regulation will expand our understanding of native and synthetic systems.

DOI: https://doi.org/10.1126/science.adw1925
ACS Appl Mater Interfaces. 2026 Apr 27.

3D-Printed, Ultrastretchable Polychloroprene Elastomers via Thiol-ene Photopolymerization.

Levi M J Moore, Maren E Summers, Ashley M Robinson, Anesia D Auguste, Reagan Elia, Jared A Gibson, Jacob C Marcischak, Johnnay A Martin, Kamran B Ghiassi.

  Polychloroprene is a foundational high-performance synthetic elastomer known for its exceptional chemical stability, resistance, and mechanical properties, making it useful in many important applications ranging from aerospace seals to medical devices. Despite its widespread use, polychloroprene is almost exclusively processed by using thermal cure agents. Herein, we report the first-ever successful ultraviolet (UV) curing and three-dimensional (3D) printing of polychloroprene networks. Leveraging thiol-ene click chemistry, solid polychloroprene was dissolved in a solvent and UV-cured with varied concentrations and architectures of thiol cross-linkers. Upon solvent evaporation, the resulting cross-linked polychloroprene networks exhibit ultrahigh extensibility, with strain at break values approaching 2000%. Significantly, their thermal properties show only marginal differences from those of the uncured material, confirming the preservation of the intrinsic polychloroprene characteristics. We demonstrate the potential of this new material platform using photorheology experiments, as well as successful 3D printing of complex objects using a commercial digital light processing (DLP) system. The printed articles exhibit mechanical properties fully comparable to conventionally processed, unfilled polychloroprene rubber, achieving an ultimate tensile stress of 2.4 MPa and a strain at break of 1200%. This work overcomes a significant processing barrier, offering an avenue to additively manufacture high-performance polychloroprene structures with exceptional mechanical resilience.

Keywords:  3D printing; elastomers; polychloroprene; stretchability; thiol-ene; vat photopolymerization

DOI:  https://doi.org/10.1021/acsami.6c03614
bioRxiv. 2026 Apr 19. pii: 2026.04.16.718941. [Epub ahead of print]

PALINCODE: Recording cell lineage with ternary palindromic CRISPR bits.

Maryam Fathi, Aidan Cook, Bagheri Meisam, Tyler Curiel, Aaron McKenna.

Reconstructing complete and accurate lineage trees remains a long-standing challenge in biology. Here, we introduce PALINCODE ( Palin dromic Co ding and De coding), a system that utilizes ternary CRISPR bits (cBits) to stochastically write one of three possible states over time, permanently embedding lineage relationships in the genome. We demonstrate PALINCODE's lineage-recording potential through simulations and establish palindromic CRISPR editing in cell culture models. We show that truncated Cas9 guide sequences yield ternary outcomes at high efficiency when compared to conventional guides. Using PALINCODE, we derived lineage-recording cell lines with a theoretical coding capacity of up to 10^25 bits, enabling the generation of lineage trees 32 cell divisions deep in single-cell sequencing of 293T cells. Furthermore, we applied PALINCODE using an in vivo melanoma model to jointly read out lineage history and gene expression, enabling in vivo reconstruction of clonal evolution within tumor cell clonal populations. PALINCODE circumvents several limitations of prior CRISPR-based systems while increasing the information potential at individual CRISPR sites, creating a lineage-recording platform with higher density than many competing approaches.

DOI: https://doi.org/10.64898/2026.04.16.718941
Proc Natl Acad Sci U S A. 2026 May 05. 123(18): e2532840123

An exceptionally conductive hydrogel for all-organic, ultraflexible, and chronic neural interfaces.

Ruiqi Zhu, Zhengwei Hu, Zirui Lou, Fei Xie, Shuainan Zhao, Xuechen Jiao, Jianyu Wang, Kenjiro Fukuda, Xiaodong Chen, Wenping Hu, Hui-Ming Cheng, Xiaojian Li, Takao Someya, Xiaomin Xu.

  Chronic neural interfaces are essential for advancing brain-computer interfaces, neuroprosthetics, and neuromodulation technologies. However, a long-standing trade-off between performance and longevity persists due to the scarcity of materials that simultaneously achieve superior electrical performance, mechanical compliance, and biocompatibility. Here, we overcome this limitation with an all-organic, ultraflexible electrocorticography (ECoG) design that features a thickness of only 9 µm, achieving low electrode-tissue impedance and durability in vivo. Central to this design is a conductive hydrogel featuring an interfacial percolation (CHIP) microstructure, with tunable hydration levels and softness, achieving a highest in-plane electrical conductivity of 2,512 S cm-1. We further developed an in-plane swelling control with a dry, soft-protective etching strategy that preserves the structural integrity during hydrogel processing. The resulting all-organic ECoG array conforms to the cortical surface, minimizing foreign body response and providing exceptional signal quality, with the longest record up to 550 d.

Keywords:  conductive hydrogel; flexible bioelectronics; neural interface

DOI:  https://doi.org/10.1073/pnas.2532840123
bioRxiv. 2026 Apr 14. pii: 2026.04.11.717926. [Epub ahead of print]

Engineered Channel Asymmetry Extends Hydrogen-Bonding Networks for Proton Conduction.

Nolan P Jacob, Vincent T Silverman, Gisselle Prida Ajo, Huong T Kratochvil.

The precise and selective transport of protons across cellular membranes relies on the dynamic formation and dissipation of hydrogen-bonding networks involving water molecules, protein sidechains, and backbone carbonyls. As in aqueous solution, protons are conducted over long distances along chains of hydrogen-bonded water molecules within narrow protein pores. To engineer proton-conductive pathways, therefore, we must explicitly account for the dynamic behavior of these networks. In previous work, we showed that incorporation of polar Gln residues into hydrophobic pores drives formation of transient, single-file water wires that enable proton-selective transport. Here, we sought to enhance conduction by introducing targeted Ile-to-Ser substitutions to extend connectivity across the pore. We find that the position of Ser relative to Gln modulates sidechain dynamics and, in turn, channel hydration. Although increased polarity reduces hydrophobic length and enhances hydration, these effects alone do not explain the observed conduction rates. Instead, asymmetry in the arrangement and dynamics of polar sidechains emerges as a key determinant of proton conductivity. Together, these results demonstrate that proton conduction is governed not only by pore polarity and hydration, but also by the dynamic and asymmetric organization of hydrogen-bonding networks. This work establishes design principles for engineering proton-selective channels and reveals how asymmetry enables efficient proton transport across biological membranes.
Significance Statement: Proton transport, central to many biocatalytic and bioenergetic processes, requires exceptional selectivity, yet the governing principles remain elusive and difficult to disentangle in natural systems. Designed minimalist proton channels offer new avenues to isolate and test features hypothesized to influence proton conduction. Here, we engineered new-to-nature proton channels with increasingly polar vestibules to establish how control of the hydrogen-bonding network tunes proton conductivity. We found that the effective hydrophobic length, pore polarity, and pore hydration do not contribute significantly to proton conduction rates. Instead, we show that asymmetric sidechain dynamics are key to extending the hydrogen-bonding networks necessary for rapid proton translocation. Our results reveal new tunable parameters that must be considered in the design of proton-selective systems.

DOI: https://doi.org/10.64898/2026.04.11.717926
Nat Biomed Eng. 2026 Apr 30.

STRAIGHT-IN Dual: a platform for dual single-copy integrations of DNA payloads and gene circuits into human induced pluripotent stem cells.

Albert Blanch-Asensio, Deon S Ploessl, Benjamin B Johnson, Sara Cascione, Myrthe R M Berndsen, Nathan B Wang, Valeria V Orlova, Anna Alemany, Christine L Mummery, Kate E Galloway, Richard P Davis.

Targeting DNA payloads into human induced pluripotent stem cells (hiPSCs) typically requires multiple inefficient steps, slowing the testing of gene circuits and cell-fate programmes. Here we show that STRAIGHT-IN Dual enables simultaneous, allele-specific, single-copy integration of two DNA constructs efficiently within 1 week. STRAIGHT-IN Dual leverages the STRAIGHT-IN platform for near-scarless payload integration, facilitating the recycling of components for further modifications. Using STRAIGHT-IN Dual, we investigate how promoter choice and gene syntax influence transgene silencing and how these design features affect reporter expression and forward programming of hiPSCs into neurons, motor neurons and endothelial cells. We also incorporate a grazoprevir-inducible synthetic gene switch that complements tetracycline-inducible control, providing tunable and temporally controlled expression of different transcription factors within the same cell. STRAIGHT-IN Dual generates homogeneous engineered hiPSC populations, accelerating synthetic biology design-build-test cycles in stem cells and enabling controlled comparisons of circuit performances.

DOI: https://doi.org/10.1038/s41551-026-01677-9
RSC Adv. 2026 Apr 20. 16(23): 21307-21319

Enhanced electrochemical and thermoelectric performance of bacterial cellulose-based composite aerogels via multi-component reinforcement.

Qi Xiao, Enhao Xie, Zhe Gao, Yuhan Wang, Wen Chen, Wei Fan, Jahongir Akhmedov, Ulugbek Gulbaev.

Flexible wearable electronics demand multifunctional materials with robust mechanical properties, high conductivity, and sensing capabilities. However, existing bacterial cellulose (BC)-based aerogels suffer from poor mechanical stability and limited electrical performance. Here, we report a synergistic, multi-component reinforcement strategy for fabricating high-performance BC-based composite aerogels. By incorporating sodium alginate (SA) as a toughening modifier and integrating dual conductive polymers (poly(3,4-ethylenedioxythiophene) (PEDOT) and polyaniline (PANI)), we construct an ionically cross-linked network via Ca2+ chelation. The optimized aerogel (BC : PEDOT = 2 : 1, 30% SA, 4% PANI) demonstrates remarkable multifunctional performance: a specific capacitance of 37.09 F g-1 with 98.3% retention after 10 000 cycles, superior thermoelectric properties (Seebeck coefficient: 0.7 mV K-1, electrical conductivity: 4.5 S cm-1, power factor: 220.5 µW m-1 K-2), and stable pressure-responsive behavior (18.5 mV and 6.8 µA at 5 kPa). The composite aerogel exhibits good mechanical properties, with a stress of up to 9.6 kPa at 100% compressive deformation after 100 cycles. The Ca2+-mediated ionic cross-linking significantly enhances mechanical robustness compared to pristine BC aerogels, while the synergistic combination of PEDOT and PANI creates continuous electron-transport pathways. This work demonstrates that rational design of multi-component systems can overcome the traditional trade-off between mechanical and electrical properties in BC-based materials, offering a promising approach for next-generation flexible electronics, including self-powered sensors and wearable energy storage devices.

DOI: https://doi.org/10.1039/d6ra01008c
ACS Appl Mater Interfaces. 2026 Apr 28.

Soft, Skin-Conformal Electronic Interfaces for Multimodal Biosignal Monitoring and Transcutaneous Stimulation.

Md Saifur Rahman, Ziyu Zhu, Nicholas B Abadie, Kailash Pillai, Adam Reyes, Luke McKinley, Creed G Bielss, Salina Teng, Jie Zhao, Dimitry G Sayenko, Limei Tian.

  Soft, stable, and high-performance skin-electrode interfaces are essential for continuous electrophysiological recording and transcutaneous electrical stimulation. Conventional gel electrodes suffer from dehydration, unstable skin-electrode contact, reduced recording quality, and limited stimulation efficiency during prolonged use. This paper reports a soft, mixed-conducting nanocomposite electrode composed of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) integrated with hygroscopic and ionic dopants. The synergistic formulation enhances mixed ionic-electronic conduction, mechanical softness, and long-term hydration stability. A simple micromolding process enables scalable fabrication of conformal, freestanding electrodes that adhere seamlessly to the skin. The optimized composition achieves an excellent balance between conductivity and softness, exhibiting approximately a 20-fold lower interfacial impedance and a 2.6-fold higher charge injection capacity compared to gel electrodes. As a result, these nanocomposite electrodes deliver higher signal-to-noise ratios in electrocardiography and electromyography recordings and enhanced bioimpedance sensitivity and achieve a 2-fold expansion of the stimulation window. This nanocomposite design establishes a versatile materials platform for soft, durable, and high-fidelity bioelectronic interfaces, enabling advances in wearable sensing and neuromodulation technologies.

Keywords:  PEDOT:PSS; conductive nanocomposite; electrophysiological recording; ionic−electronic conduction; soft electronics; transcutaneous electrical stimulation

DOI:  https://doi.org/10.1021/acsami.6c02518
bioRxiv. 2026 Apr 15. pii: 2026.04.13.718069. [Epub ahead of print]

Lifetime-based multiplexed detection of viral RNA using fluorogenic aptamers.

Yuan-I Chen, Yu-An Kuo, Yujie He, Naseem Siraj, Emile J Batchelder-Schwab, Yin-Jui Chang, Siem Yonas, Yuting Wu, Zhenglin Yang, Anh-Thu Nguyen, Sohyun Kim, Yi Lu, Chengde Mao, Pengyu Ren, Hsin-Chih Yeh.

Fluorogenic aptamers (FAPs) are emerging molecular probes for viral RNA and DNA sensing. However, their use in multiplexed nucleic acid sensing has been hindered by cross-reactivity and overlapping emission spectra. Here we address these limitations by introducing a fluorescence-lifetime-based multiplexed detection strategy using variants of the DNA fluorogenic aptamer Lettuce that exhibits distinct fluorescence lifetimes when complexed with the fluorogen TO1-biotin. To effectively evolve Lettuce for diverse lifetimes, we developed a large-scale screening platform, termed FAP-FLIM-NGS (fluorogenic ap tamer-based fluorescence lifetime imaging m icroscopy on n ext- g eneration s equencing chips), which measures the fluorescence lifetimes of ∼10 4 Lettuce /TO1-biotin complexes directly on an Illumina MiSeq flow cell. Using this approach, three variants with markedly different lifetimes were identified: a single mutant (smC14T, 6.0 ns) and two double mutants (dmA5T/C14T, 5.2 ns, and dmA5T/T22A, 4.4 ns). To demonstrate the utility of these Lettuce variants in multiplexed detection, a set of split Lettuce probes targeting viral RNA fragments derived from SARS-CoV-2, MERS-CoV, and influenza A were designed and tested. Phasor plot analysis confirmed that these probes can robustly distinguish individual targets as well as mixtures containing any two or all three targets purely based on distinct fluorescence lifetimes of probes, thereby overcoming the challenges of cross-reactivity and spectral overlap. Beyond this proof of concept, our findings establish a generalizable strategy for engineering FAPs with customized photophysical properties, opening new avenues for next-generation diagnostics and molecular sensing technologies.

DOI: https://doi.org/10.64898/2026.04.13.718069
Nat Commun. 2026 Apr 30.

Wood that bonds itself via homologous adhesion through cellulose reconstitution.

Yuan Sun, Yang Liu, Long Bai, Shouxin Liu, Zhangmin Wan, Zhaolin Yang, Liwen Yu, Siqi Huan, Chengyu Wang, Zhiguo Li, Yi Lu, Orlando J Rojas.

Wood panels are extensively applied in furniture, construction fields, where their versatility and cost-effectiveness make them indispensable, but their assembly relies on adhesives that emit toxic formaldehyde, demand energy-intensive curing, and form weak interfacial bonds. Inspired by wood's self-repair via cellulose microfibril reorganization, we develop a cellulose-based homologous active adhesive (HAA) derived from wood components. HAA cures under ambient hydration, eliminating toxic emissions and reducing energy consumption by >80%. Its mechanism activates wood surface hydroxyl groups and regenerates cellulose to create a seamless transition layer that enhances load transfer and resistance. This architecture enables specific bonding strength up to 100× greater than conventional adhesives, despite ultra-low solid content (<5%). Using molecular dynamics simulations, AFM nanomechanics, spectroscopy, and life-cycle assessment, we reveal that HAA outperforms commercial resins, offering pot life >30 days, full biodegradability, and >70% lower environmental impacts. HAA establishes a biomimetic, circular pathway for sustainable, high-strength wood bonding.

DOI: https://doi.org/10.1038/s41467-026-72609-z
Trends Biotechnol. 2026 Apr 29. pii: S0167-7799(26)00085-5. [Epub ahead of print]

One-pot expression of an oligoclonal nanobody-based antivenom in growth-decoupled Escherichia coli.

Patrick Stargardt, Anne Ljungars, David Scheich, Nico Lingg, Emil S Elmose, Shirin Ahmadi, Florian Simon, Alois Jungbauer, Juergen Mairhofer, Andreas H Laustsen.

  Oligoclonal VHH mixtures targeting distinct epitopes offer therapeutic benefits in mitigating complex diseases, including cancer, infectious diseases, and snakebite envenoming. However, current production strategies rely on separate expression and purification of individual VHHs, followed by downstream mixing, resulting in high costs. We present a cocultivation approach for producing an experimental recombinant antivenom using growth-decoupled Escherichia coli strains. Six different cell lines were generated by transforming the same host with different VHH genes. The cell lines displayed high-yield extracellular secretion in microtiter plate and 1-l bioreactor cultivations, and cocultivation at defined inoculation ratios yielded oligoclonal VHH mixtures approaching target compositions. This strategy enables one-pot manufacturing with minimal downstream processing and predictable composition. A techno-economic assessment based on obtained titers and two-step purification indicates reduced per-treatment costs compared with Chinese Hamster Ovary cells produced IgG-based antivenoms. Our findings offer an alternative to conventional oligoclonal VHH production for multivalent therapeutics requiring broad neutralization, including recombinant antivenoms.

Keywords:  V(H)H; growth-decoupled production; one-pot manufacturing; recombinant snakebite antivenoms; snakebite envenoming; techno-economic analysis

DOI:  https://doi.org/10.1016/j.tibtech.2026.02.022
Nat Mater. 2026 Apr 29.

Fibrillar adhesion dynamics govern the timescales of nuclear mechano-response via the vimentin cytoskeleton.

Amy E M Beedle, Vivek Sharma, Jorge Oliver-De La Cruz, Anuja Jaganathan, Aina Albajar-Sigalés, F Max Yavitt, Kaustav Bera, Ion Andreu, Ignasi Granero-Moya, Dobryna Zalvidea, Zanetta Kechagia, Gerhard Wiche, Xavier Trepat, Johanna Ivaska, Kristi S Anseth, Vivek B Shenoy, Pere Roca-Cusachs.

The cell nucleus is continuously exposed to external signals, of both chemical and mechanical nature. To ensure proper cellular response, cells need to regulate the transmission, timing and duration of these signals. Although such timescale regulation is well described for chemical signals, whether and how it applies to mechanical signals reaching the nucleus is still not fully understood. Here we demonstrate that the formation of fibrillar adhesions locks the nucleus in a mechanically deformed conformation, setting the mechano-response timescale to that of fibrillar adhesion remodelling (~1 h). This process encompasses both mechanical deformation and associated mechanotransduction (such as via YAP), in response to both increased and decreased mechanical stimulation. The underlying mechanism is the anchoring of the vimentin cytoskeleton to fibrillar adhesions and the extracellular matrix through plectin 1f, which maintains nuclear deformation. Our results reveal a mechanism to regulate the timescale of mechanical adaptation, effectively setting a low-pass filter to mechanotransduction.

DOI: https://doi.org/10.1038/s41563-026-02590-x