bims-enlima 2026-02-01 papers

bims-enlima

Biomed News

on Engineered living materials

Issue of 2026–02–01
35 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool

Modular parallel plate flow chamber with tunable substrate mechanics and defined shear stress.
Artificial Symbiosis for Bulk Production of Bacterial Cellulose Composites.
Quinone-Grafted Chitosan Polymers Enhance Microbial Extracellular Electron Transfer for Living Bioelectronic Devices.
Programming Hydrogel Mechanics via Sequence-Controlled Polymerization Using Peptide Self-Assembly.
Peptide-reinforced, photocrosslinkable PEG-based hydrogels.
Mechanochemical regulation of organoid morphogenesis: Integrated signaling circuits in engineered microenvironments.
Mistletoe- and Mussel-Inspired Fabrication of Hierarchically Structured Protein-Cellulose Scaffolds From Biomolecular Condensates.
Synergizing network topology and solvent compatibility for gels with hyperelasticity and omniadhesion.
DNA-Driven Liquid-Liquid Phase Separation from Cellular Condensates to Programmable Synthetic Systems.
Rubber-like DNA hydrogel enabled by fast-shrinking-induced entanglement.
Toward Dynamic Liquid Cell Scaffold: Photoreversible Ion Gels Exhibiting Light-Induced Sol-Gel Transitions.
Biotechnological Control of Hydrogel Properties via Recombinant Protein Molecular Weight Engineering.
Liquid Metal-Reinfored Hierarchically Aligned Double-Network Hydrogels: Ultrahigh Crack/Fatigue Resistance and Strain‑Responsive Sensing.
Physically structured emulsion-filled gels based on Euglena-xanthan depletion mixtures for 3D printing.
Transient pH changes drive vacuole formation in enzyme-polymer condensates.
Polyanion Chemistry Engineers Ternary RNA Nanoparticle Structure/Function from the Inside-Out.
The Coli Toolkit (CTK): An Extension of the Modular Yeast Toolkit for Use in E. coli.
Scalable and multiplexed recorders of gene regulation dynamics across weeks.
Multiphysics-Driven Assembly of Biomimetic Vesicles.
Translating Nature's Design Rules: How Catalysis and Life Science Guide Molecular Catassembly.
Tyrosinase Cross-Linked PEG Hydrogels with DAT and DATT as Artificial Substrates: Design, Structure, and Functions.
Optofluidic three-dimensional microfabrication and nanofabrication.
One-Pot Strategy to Prepare Structurally Colored Alginate Dispersions for Functional Applications.
Bioinspired Programmable Biaxial Rolling Gel Sheets for Complex 3D Morphing.
Controlling plastic behavior with light.
Protein-Delivering Polyelectrolyte Complex Hydrogels: Structure, Swelling and Dissolution Characteristics, and Release Behavior.
Deriving genetic codes for molecular phenotypes from first principles.
Bioinspired Ultratough and Rapidly Responsive Hydrogels Empower Silent Communication.
Development of Organogel-AFPT System for Encapsulation and Cryopreservation of Yarrowia lipolytica.
Friction-controlled reentrant aging and fluidization in granular materials.
van der Waals Nanochemical Reactors.
Behavioral tuning of spider silk thread stiffness circumvents biomaterial trade-offs.
PEGylated DNA Helper Molecule-Assisted Self-Assembly of Polyelectrolyte Complex Micelles.
Coordination of cell organelles to promote metabolon formation.
Lipid Nanoparticle Database towards structure-function modeling and data-driven design for nucleic acid delivery.

Biomed Microdevices. 2026 Jan 29. 28(1): 8

Modular parallel plate flow chamber with tunable substrate mechanics and defined shear stress.

Bryan J Ferrick, Jason P Gleghorn.

  Cells integrate multiple mechanical cues simultaneously, yet most in vitro models examine extracellular matrix (ECM) stiffness and fluid shear stress (FSS) in isolation, limiting our understanding of mechanotransduction. We developed a parallel plate flow chamber with a polyacrylamide (PAA) substratum enabling independent, tunable control of substrate stiffness and FSS using readily available materials. We confirm that the PAA substratum has controllable mechanical properties that support the growth of Madin-Darby canine kidney epithelial cells across a range of stiffnesses. Furthermore, the flow chamber design accommodates the volumetric equilibrium swelling of the gel, maintaining a predictable fluid channel height that allows for the application of controlled fluid shear stress to cells within the device, confirmed through particle image velocimetry of perfused microspheres. Single flow chambers support the growth of sufficient cellular numbers for endpoint analyses, such as Western blots. Finally, quantitative analysis of F-actin organization revealed that substrate stiffness and FSS synergistically increase filament length with independent effects on filament width, demonstrating the ability and usefulness of this model as a tool for studying the effect of multiple concurrent forces on cell behavior.

Keywords:   In Vitro Models for Mechanotransduction; 2D Microfluidic flow chamber; ECM Stiffness; Fluid Shear Stress

DOI:  https://doi.org/10.1007/s10544-025-00787-6
Adv Mater. 2026 Jan 26. e14125

Artificial Symbiosis for Bulk Production of Bacterial Cellulose Composites.

Kui Yu, Sing Teng Chua, Ran Zhao, Alyssa Smith, Michael Kühl, Alison G Smith, Tom Ellis, Silvia Vignolini.

  Symbiotic relationships between micro-organisms are key to the function of all global ecosystems. Here we extrapolate this concept for biomaterial fabrication by creating artificial symbiotic relationships between species that are usually not grown synergistically in nature. Specifically, we combine the cellulose-producing bacterium Komagataeibacter hansenii and the green microalga Chlamydomonas reinhardtii to obtain bulk growth of bacterial cellulose. Usually, bacterial cellulose is produced as floating pellicles at the air-liquid interface of the growing media, because free oxygen, together with the nutrients in the culture medium, is required for the bacteria to synthesize the cellulose fibers. In the co-culture, bacterial cellulose production can be achieved in bulk beyond the spatial restriction of the air-liquid interface as the motile microalgae with photosynthetic activities act as oxygen-generating sites within the culture medium. In exchange, the highly porous and mechanically robust scaffold provided by the cellulose allows the algal-bacterial community to form a bio-composite up to several centimeters in thickness. We demonstrate that this symbiotic growth platform allows the simultaneous production of bulk bacterial cellulose in static incubation conditions, taking up an arbitrary and yet tunable 3D shape, dependent on the geometry of the culture vessel.

Keywords:  bacterial cellulose; bacterial cellulose nanocrystals; biofilm; co‐culture; immobilization; living materials; microalgae

DOI:  https://doi.org/10.1002/adma.202514125
Adv Mater. 2026 Jan 29. e18817

Quinone-Grafted Chitosan Polymers Enhance Microbial Extracellular Electron Transfer for Living Bioelectronic Devices.

Xinyuan Zuo, Siliang Li, Abdullah Alazmi, Fiona Chen, Ravindra Saxena, Harsh Vardhan, Titus Szobody, Jaime Guel, Caroline Ajo-Franklin, Rafael Verduzco.

  Microbial bioelectronics using electroactive bacteria provide robust and sustainable solutions for sensing, power generation, and chemical production. While most rely on a limited group of Gram-negative bacteria, Gram-positive species offer devices with additional functionality and broader environmental ranges. However, their thick, nonconductive cell walls hinder efficient extracellular electron transfer (EET). Here, a living bioelectronic device using a redox-active polymer to encapsulate Gram-positive bacteria near an electrode while simultaneously enhancing EET is reported. The redox-active polymer NQ-Chit contains naphthoquinone redox groups grafted onto a chitosan backbone and can be ionically cross-linked to produce redox- active hydrogels. To fabricate living bioelectronic devices, NQ-Chit is blended with the Gram-positive bacterium Lactiplantibacillus plantarum, deposited on an electrode, and ionically cross-linked in situ. The NQ-Chit hydrogel enhances EET current compared to both pure Chit-encapsulated bacteria and planktonic bacteria with NQ-Chit-coated electrodes, and Michaelis-Menten kinetics can describe the dependence of EET current on the concentration of quinone units. The devices remain functional after multiple medium exchanges. Additionally, the redox polymer enhances EET across diverse electroactive bacteria and enables a proof-of-concept for detecting environmental chemicals. This work demonstrates that encapsulating electroactive bacteria with redox-active hydrogels enhances EET and can be implemented in practical bioelectronic devices.

Keywords:  bioelectronics; biosensors; redox‐active hydrogels; redox‐active polymers

DOI:  https://doi.org/10.1002/adma.202518817
J Am Chem Soc. 2026 Jan 29.

Programming Hydrogel Mechanics via Sequence-Controlled Polymerization Using Peptide Self-Assembly.

Abolfazl S Moghaddam, Maahi Zaman, Sz-Chian Liou, E Thomas Pashuck.

Hydrogels often have poor mechanical properties due to their high water content and low polymer concentration, which limits their utility in applications that require them to withstand applied forces. Inspired by natural biopolymers such as collagen and actin, which form highly extended fibrillar networks that stiffen biological tissues, we developed a modular strategy that utilizes self-assembling peptides to direct the formation of covalently polymerized diacetylene networks in hydrogels. By systematically tuning peptide sequences, we precisely controlled the supramolecular organization and molecular orientation within the self-assembled nanofibers. This optimization enabled efficient topotactic polymerization of diacetylene moieties within the self-assembling peptides. Peptide sequences that readily promoted polymerization formed hydrogels with superior viscoelastic properties. Incorporation of these diacetylene peptide amphiphiles (DA-PAs) into covalently cross-linked poly(ethylene glycol) (PEG) hydrogels increased their mechanical stiffness 200-fold, while increasing viscous dissipation over 1,000 times. Modifying the chemical structure of the PEG cross-linker tuned the interfacial interactions between the covalent PEG and DA-PA networks, modulating stiffness by almost an order of magnitude. Since the DA-PAs readily dissolve in water prior to polymerization, they can be incorporated into most hydrogel systems. Adding them to alginate hydrogels led to an almost 20-fold increase in the hydrogel stiffness. This approach, merging peptide-driven supramolecular chemistry with precise covalent polymerization, provides powerful and versatile pathways for fabricating mechanically robust materials that offer new insights into how hierarchical structures can be used to improve hydrogel mechanics.

DOI: https://doi.org/10.1021/jacs.5c12182
RSC Appl Polym. 2026 Jan 05.

Peptide-reinforced, photocrosslinkable PEG-based hydrogels.

Sam Russell, Daseul Jang, Jessica Thomas, Patrick Grysan, Linus Sprandl, Markus Biesalski, LaShanda T J Korley, Nico Bruns.

Hydrogels are polymer networks that swell in aqueous solvents. These materials have applications in many fields, including drug delivery, tissue engineering, and soft robotics. For example, polyethylene glycol (PEG) diacrylate is often used as a light-curable crosslinker for the synthesis of PEG-based hydrogels, e.g., in bioinks for 3D printing. However, a common limitation of PEG hydrogels is their typically poor mechanical properties, particularly when in a swollen state. The mechanical strength of natural polymeric materials, such as spider silk and collagen, arises from the formation of hierarchical secondary protein structures that unfold under mechanical load. Here, we present a bio-inspired approach to reinforcing PEG-based hydrogels that mimics these hierarchical structures by incorporating poly(β-benzyl-l-aspartate) (PBLA) blocks between cross-linking end groups and PEG chain segments. We used this peptide-containing crosslinker in combination with a small hydrophilic comonomer, 2-hydroxyethyl acrylate, to synthesise PHEA-linked by-(PBLA-b-PEG-b-PBLA) co-networks with tailored compositions, yielding improved and tailorable mechanical properties. This approach affords hydrogels with increased strength and toughness while retaining the networks' swelling ability. This research presents a promising avenue for developing robust photocrosslinkable hydrogels with broad practical applications.

DOI: https://doi.org/10.1039/d5lp00335k
Mater Today Bio. 2026 Apr;37 102782

Mechanochemical regulation of organoid morphogenesis: Integrated signaling circuits in engineered microenvironments.

Xinxin Zhang, Yuanyuan Zhao, Lina Mao, Qiangsong Wang, Pengyu Huang.

  Organoid morphogenesis is orchestrated by complex mechanical interactions between cells and their microenvironment. Recent evidence highlights the critical role of mechanical stimuli-including fluid shear stress, axial tensile and compressive forces, extracellular matrix (ECM) stiffness, and viscoelasticity-in integrating through specialized mechanotransduction hubs to regulate spatial and temporal morphogenetic programs. These mechanical cues are decoded by interconnected signaling architectures, including the MAPK/PI3K-Akt pathways mediating fluidic forces, the Wnt/β-catenin and Hippo-YAP/TAZ cascades responding to axial forces and ECM rigidity, and the integrin-β1-tensin-1-YAP axis interpreting ECM viscoelastic properties. These interconnected networks establish hierarchical control over organoid proliferation, lineage specification, and tissue patterning across diverse culture systems, spanning static elastic substrates to dynamic viscoelastic matrices with tunable stress relaxation profiles. Beyond cytoplasmic signaling, emerging studies identify nuclear mechanotransduction as a central integrative layer that converts mechanical inputs into stable transcriptional and epigenetic outcomes. Mechanical forces transmitted via the cytoskeleton-LINC complex reshape nuclear mechanics through Lamin A-dependent regulation of nuclear stiffness, directly remodel chromatin accessibility, and modulate mechanosensitive transcriptional regulators. Through this nucleus-centred mechanism, transient mechanical cues are encoded as persistent gene expression programmes that govern cell fate specification, tissue layering, and functional compartmentalisation in organoids. This review systematically maps the mechanobiological logic underlying organoid development across three analytical dimensions: molecular decoding of mechanical inputs, cellular-scale integration of mechanotransduction signals, and emergent tissue-level patterning. By elucidating self-reinforcing feedback loops between matrix biophysics, nuclear mechanics, and chromatin organisation, we propose an engineering framework for designing biomimetic microenvironments. This approach enables the development of next-generation organoid platforms with enhanced architectural fidelity and physiological relevance, particularly through spatiotemporal control of viscoelastic memory and dynamic mechanical conditioning.

Keywords:  Cellular microenvironment; Extracellular matrix; Mechanotransduction; Morphogenesis; Nuclear mechanotransduction; Organoid

DOI:  https://doi.org/10.1016/j.mtbio.2026.102782
Adv Mater. 2026 Jan 28. e20827

Mistletoe- and Mussel-Inspired Fabrication of Hierarchically Structured Protein-Cellulose Scaffolds From Biomolecular Condensates.

Hamideh R Alanagh, Seyed Mohammad Amin Ojagh, Arman Jafari, Xinyu Zhan, Tara Sprules, Alexandre Poulhazan, Houman Savoji, Adam G Hendricks, Theo G M van de Ven, Matthew J Harrington.

  Nature's ability to produce hierarchical materials via biomolecular self-assembly can inspire bioinspired avenues to advanced materials using biorenewable components and water as a solvent. Recent advances indicate that biomolecular condensates are important precursor phases for fabricating biological materials. Here, we leverage recent findings on the role of malleable biomolecular phases from both animal and plant systems to develop a synergistic mussel- and mistletoe-inspired approach for fabricating protein-cellulose composite scaffolds possessing tunable hierarchical structure. We demonstrate that recombinant mussel foot protein-1 (rMfp-1), undergoes controlled phase separation when mixed with surface-functionalized anionic cellulose nanorods, forming condensates with characteristic core-shell morphology. Using a facile approach based on freeze-drying of suspensions, we produce freestanding protein-cellulose composite scaffolds possessing tunable porous structures with potential as scaffolds for tissue engineering. Through a cross-disciplinary approach combining various spectroscopic and imaging modalities, we gain mechanistic insights into the role of intermolecular interactions and physical processes in guiding this process. These findings highlight that hierarchically structured materials can be fabricated simply via multi-component phase separation. This work establishes a framework for understanding and controlling bio-inspired material fabrication, offering a strategy to engineer materials with tunable structure and properties that bridge biomaterials research and emerging directions in synthetic biology.

Keywords:  coacervates; functionalized cellulose; hierarchical; mussel foot protein; phase separation; protein condensates; scaffold

DOI:  https://doi.org/10.1002/adma.202520827
Sci Adv. 2026 Jan 30. 12(5): eaec7718

Synergizing network topology and solvent compatibility for gels with hyperelasticity and omniadhesion.

Qiqi Xue, Xinyu He, Jincheng Lei, Wei Hong, Canhui Yang.

In polymeric gels, hyperelasticity and strong adhesion are often required but difficult to achieve simultaneously. Here we propose a principle of hyperelastic and omniadhesive gels composed of polymer networks with long dangling chains and sufficient good solvents. The molecules of good solvents screen off interchain interactions for hyperelasticity. The long dangling chains disentangle and adsorb to substrate for strong adhesion. We synthesized such gels by controlling the polymerization kinetics. When a monomer solution is partially cured, some monomers form a network and others form the solvent. The resulting gel, termed homogel, consists of a polymer network with enormous dangling chains and solvent of identical chemistries. An interval exists where the dangling chains are long and disentangled substantially, and the homogel exhibits both hyperelasticity and omniadhesion. We demonstrated such a gel with a hysteresis of 4.1% (stretch = 10) and adhesion energy of ~510 joules per square meter. The principle is generic and applicable to gels of different types.

DOI: https://doi.org/10.1126/sciadv.aec7718
ACS Appl Bio Mater. 2026 Jan 26.

DNA-Driven Liquid-Liquid Phase Separation from Cellular Condensates to Programmable Synthetic Systems.

Sanjay Kosara, Abhijit Biswas, Amit K Yadav, Raghu Solanki, Dhiraj Bhatia.

  Liquid-liquid phase separation (LLPS) compartmentalizes biological systems into dynamic, membraneless condensates that regulate diverse cellular functions. Although protein and RNA-mediated LLPS have dominated research, DNA increasingly emerges as an active driver of phase separation rather than a passive structural scaffold. DNA-driven condensates orchestrate critical nuclear processes, from chromatin organization and transcriptional regulation to genome stability and innate immune responses. Yet LLPS principles extend beyond biology: programmable DNA nanostructures now enable synthetic droplets and hydrogels with tunable mechanical properties, opening pathways to biomaterials, diagnostics, and synthetic cells. Here we synthesize current understanding of DNA-mediated LLPS across biological and synthetic domains, emphasizing five underappreciated topics: (1) DNA's active driving role in LLPS through charge and topology; (2) reversible DNA aggregation and aggregate-to-condensate transitions, distinct from irreversible protein misfolding; (3) non-Fickian transport mechanisms including ballistic wave diffusion triggered by molecular recognition; (4) single-molecule mechanical characterization revealing state-dependent material properties; and (5) the multiscale complexity of cellular DNA condensation shaped by topological constraints and hierarchical organization. We highlight emerging single-molecule technologies, optical tweezers, and scanning probe microscopy that directly measure condensate mechanics and state transitions with unprecedented resolution. This integrated perspective bridges fundamental biophysics of natural DNA condensates with rational engineering principles for programmable synthetic systems, providing a blueprint for therapeutic and biotechnological applications.

Keywords:  DNA droplets; DNA hydrogel; artificial DNA junctions; biomolecular condensates; liquid−liquid phase separation; synthetic cells

DOI:  https://doi.org/10.1021/acsabm.5c02505
Nat Commun. 2026 Jan 28.

Rubber-like DNA hydrogel enabled by fast-shrinking-induced entanglement.

Zi'an Lin, Shuran Fang, Qingshan Huang, Xiachu Xiao, Jiali Jiang, Long Zhao, Guojiao Wu, Guojie Zhang, Zhuolei Zhang, Yuzhou Wu.

Biomass DNA holds immense potential as a sustainable material, but the scalable production of robust DNA materials with sufficient mechanical strength remains an essential challenge. Herein, we report a Fast-Shrinking-Induced Entanglement (FaSIE) process to achieve rubber-like hydrogels solely composed of DNA (stiffness >800 kPa, toughness >5 MJ/m3, and stretchability > 1000%). Fast shrinking kinetic restricts the chain relaxation, while the ultra-long chain feature of biomass DNA further suppress chain reptation. This synergistic effect enables substantial enhancement of entanglement density, exceeding the threshold required for high mechanical strength. We highlight the broad applicability of this strategy for high-resolution 3D printing of mechanically robust DNA hydrogels and the fabrication of DNA based soft magnetic robots. This approach paves the way for the large-scale production of resilient hydrogel materials derived from biomass DNA for versatile applications.

DOI: https://doi.org/10.1038/s41467-026-68363-x
Macromol Rapid Commun. 2026 Jan 28. e00909

Toward Dynamic Liquid Cell Scaffold: Photoreversible Ion Gels Exhibiting Light-Induced Sol-Gel Transitions.

Aya Saruwatari, Yuji Kamiyama, Ryota Tamate, Jun Nakanishi, Takeshi Ueki.

  Reversible sol-gel transitions are difficult to achieve in conventional water-swollen hydrogels in open aqueous environments, because polymer chains dissolve or diffuse once the network disassembles. Here, we present a proof-of-concept to overcome this limitation by introducing a water-immiscible and non-cytotoxic ionic liquid (IL) phase that confines polymer networks and prevents dissolution during reversible phase transitions. We report a photoreversible ion gel that crosses the rheological boundary (tan δ ∼ 1) under light, enabling reversible sol-gel switching within this closed IL environment. The material integrates an ABC triblock copolymer, P(AzoAm-r-NIPAm)-b-PBuA-b-PSt, with a solvent-quality-tunable blend of non-cytotoxic ILs ([P4,4,4,1][TFSI]/[P8,8,8,8][TFSI]). The photoresponsive A-block, P(AzoAm-r-NIPAm), exhibits a polarity-dependent solubility change with the cis/trans isomerization of azobenzene, providing a reversible light-controlled self-assembly. Time-resolved rheology confirmed repeated crossings of tan δ = 1 under alternating UV-vis illumination at 52°C. The switching mechanism is governed by the lifetime of reversible junctions, consistent with transient network theory. In addition, hMSCs adhered to and spread on the ion gel at 37°C, indicating the cytocompatibility of the ion gel itself. This light-programmable, water-immiscible ion gel has the potential to provide a reversible liquid-solid mechanical cue for next-generation mechanobiology.

Keywords:  azobenzene; block copolymers; gels; ionic liquids; mechanobiology; photoreversible gelation; stimuli responsive materials

DOI:  https://doi.org/10.1002/marc.202500909
Macromol Biosci. 2026 Jan;26(1): e00575

Biotechnological Control of Hydrogel Properties via Recombinant Protein Molecular Weight Engineering.

Domenic Schlauch, Jan Peter Ebbecke, Amelie Paula von Alwörden, Dörte Solle, Selin Kara, Antonina Lavrentieva, Iliyana Pepelanova.

  Hydrogels based on natural polymers are widely used in 3D cell culture and tissue engineering due to their biocompatibility and tunability. In this work, recombinant collagen-derived proteins of defined molecular weights were designed and tested as precursors for methacrylated, photocrosslinkable hydrogels. Proteins of 25.6 kDa, 58 kDa, and 89.2 kDa were recombinantly expressed in Komagataella phaffii, methacrylated, and photocrosslinked to form well-defined hydrogels. A Design of Experiments (DoE) strategy was employed to quantify the effects of degree of functionalization (DoF) and precursor molecular weight on hydrogel stiffness, deformability, and swelling. For the first time, it was reported that both the DoF and molecular weight of recombinant proteins used for hydrogel fabrication significantly influence hydrogel properties. The molecular weight effects were most pronounced at lower chain lengths. Predictive models generated from the DoE revealed non-linear and interactive contributions of both parameters, while mixed-material formulations suggested non-additive behavior beyond the fitted design space. Additionally, biocompatibility for all materials was shown by live-dead staining of cells seeded onto the crosslinked materials. The results demonstrate that recombinant protein chain length can be used as a powerful design parameter to modulate hydrogel mechanics. Such materials not only enable xeno-free cultivation but also provide a biotechnological route toward rationally engineered biomaterials for diverse applications.

Keywords:  GelMA; design of experiments; hydrogel; molecular weight; recombinant gelatin

DOI:  https://doi.org/10.1002/mabi.202500575
Small. 2026 Jan 30. e12709

Liquid Metal-Reinfored Hierarchically Aligned Double-Network Hydrogels: Ultrahigh Crack/Fatigue Resistance and Strain‑Responsive Sensing.

Pengcheng Cui, Jiadong Chen, Rouling Chen, Wei Chang, Kun Chen, Chao Yuan, Xiangke Wang, Suhua Wang.

  Soft hydrogels are promising for wearable stretchable devices due to their flexibility, stretchability, and biocompatibility, but most existing soft hydrogels suffer from crack propagation and fatigue failure. Inspired by the structure-property relationships of biological tissues, we developed a pre-alignment and subsequent cross-linking strategy to fabricate a hierarchically anisotropic double-network (DN) hydrogel that exhibits remarkable toughness, exceptional fatigue resistance, and high conductivity. The anisotropically aligned polymer network, synergistically combined with deformable liquid metals (LM) particles, enables efficient stress transfers and crack propagation suppression. The hydrogels exhibit a high fracture energy of 60.6 kJ m-2 and an ultrahigh fatigue threshold of 5560 J m-2, while maintaining a human skin-matching modulus of 1.3 MPa. Furthermore, the LM particles impart relatively high conductivity, enabling the use of composite hydrogels as stretchable sensor devices for stable and reliable motion monitoring. This study provides a new strategy for fabricating anisotropic hydrogels with superior mechanical and conductive properties, advancing their applications in wearable electronics and soft robotics.

Keywords:  anisotropic hierarchical structure; composite hydrogel; crack resistance; fatigue‐free; stretchable sensing

DOI:  https://doi.org/10.1002/smll.202512709
Carbohydr Polym. 2026 Mar 15. pii: S0144-8617(25)01640-6. [Epub ahead of print]376 124856

Physically structured emulsion-filled gels based on Euglena-xanthan depletion mixtures for 3D printing.

Shuwei Tang, Guangxin Feng, Lu Xu, Jinjie Tian, Yijun Liu, Zichao Li.

  The development of sustainable 3D-printable food systems requires soft materials that exhibit shear-thinning behavior during extrusion while maintaining structural integrity post-deposition. Here, we report a novel 3D-printable emulsion-filled gel system fabricated via in situ emulsification within a physically structured matrix formed by depletion interactions between Euglena gracilis biomass particles and xanthan gum (XG) polymers. Rheological analysis showed that these depletion interactions in aqueous dispersions produced weak colloidal gels with tunable viscoelasticity depending on the particle-to-polymer ratio. Incorporation of 40 wt% vegetable oil into the depletion mixtures through low-shear homogenization yielded stable, self-supporting emulsion-filled gels suitable for 3D printing. Interfacial measurements revealed that water-soluble components released from E. gracilis acted as endogenous emulsifiers, facilitating the formation and stabilization of finely dispersed oil droplets within the colloidal matrix. Large amplitude oscillatory shear (LAOS) measurements demonstrated that the embedded oil droplets contributed to increased gel strength and mechanical resilience, thereby enhancing extrudability and shape fidelity during 3D printing. This physically driven strategy eliminates the need for additional thermal or chemical treatments to produce gel matrix, providing a sustainable platform for developing functional, biocompatible soft materials suitable for personalized nutrition, advanced food structuring, and other edible applications.

Keywords:  3D printing; Depletion mixtures; Emulsion-filled gel; Euglena gracilis; Xanthan gum

DOI:  https://doi.org/10.1016/j.carbpol.2025.124856
Nat Chem Eng. 2026 ;3(1): 47-56

Transient pH changes drive vacuole formation in enzyme-polymer condensates.

Nisha Modi, Raghavendra Nimiwal, Jane Liao, Yitian Li, Kyle J M Bishop, Allie C Obermeyer.

  Membraneless organelles are essential for cellular function. These biomolecular condensates often exhibit complex morphologies in response to biological stimuli. In vitro condensate models help elucidate how these multiphase assemblies form and their possible functions. Here we use such a model to investigate the formation of hollow internal regions, or vacuoles, within condensates in response to a pH change. Fast rates of pH decrease and larger droplet sizes promote vacuole development within the condensates. We show that vacuole formation is a non-equilibrium process driven by the diffusion-limited exchange of condensate components during a rapid pH change. We develop a physics-based model that describes how associative phase-separating systems respond to rapid changes in external conditions, specifically pH. Our qualitative model agrees with experimental results, showing that rapid pH changes shift the phase boundaries, triggering spinodal decomposition and inducing vacuole formation within the condensates. Our pH-sensitive in vitro model illustrates a mechanism of vacuole formation in associative condensates and provides insights into the regulation of multiphase condensates in vivo.

Keywords:  Bioinspired materials; Biomaterials - proteins; Chemical engineering

DOI:  https://doi.org/10.1038/s44286-025-00322-7
ACS Nano. 2026 Jan 27.

Polyanion Chemistry Engineers Ternary RNA Nanoparticle Structure/Function from the Inside-Out.

Lijun Hu, David J Peeler, Tianyi Jin, James J Doutch, Baihao Shao, Jonathan Yeow, Li Ma, Hanna M G Barriga, Jiaqing Tang, Xuan Cao, Chenchen Liu, Christopher L Grigsby, Alfredo Alexander-Katz, Robin J Shattock, Molly M Stevens.

  Formulating cationic polyplexes (PP) with polyanions as ternary polyelectrolyte nanoparticles (TNP) offers a polymeric alternative to lipid nanoparticles (LNP) for targetable nucleic acid delivery. Although TNP in vivo transport is credited to their anionic surface charge, the relationships between polyanion chemistry and TNP structural stability, protein binding, and transfection are poorly understood compared to lipid-based systems. We hypothesized that carefully engineered hydrophobic polyanions could simultaneously endow TNPs with negative surface charge and enhanced extracellular stability critical to the future development of actively targeted formulations. We synthesized chemically diverse PEGylated polyanions to coat self-amplifying RNA (saRNA) PP, systematically studying how PEG architecture and polyanion chemistry modulate TNP structure and function. In both high-throughput stability assays and Small Angle Neutron Scattering structural studies, we found that PEG5k-bl-polyanion5k yields remarkably small particles with a pH-responsive core-shell structure. We identify a lead formulation (TNP5) with moderate hydrophobicity and charge density that balances extracellular stability and intracellular unpackaging for transfection. In agreement with spectroscopic characterization and in vitro cell studies, Molecular Dynamics simulations support the hypothesis that polyanions dictate TNP function from the inside-out by excluding water from the RNA core and by exposing functional groups that modulate protein binding. Our work correlates high throughput assays and detailed neutron scattering analysis to uncover mesoscale structural differences between two- and three-component polyelectrolyte delivery systems. These screening methods and the critical balances between polymer properties they uncover establish a framework for high throughput engineering of pH-responsive nanoparticle structure/function to navigate biological barriers to RNA delivery.

Keywords:  PET-RAFT; SANS; high throughput; molecular dynamics; self-amplifying RNA; structure/function

DOI:  https://doi.org/10.1021/acsnano.5c19683
ACS Synth Biol. 2026 Jan 25.

The Coli Toolkit (CTK): An Extension of the Modular Yeast Toolkit for Use in E. coli.

Jacob Mejlsted, Erik Kubaczka, Sebastian Wirth, Heinz Koeppl.

  Genetic circuits are a cornerstone of synthetic biology, enabling programmable control of cellular behavior for applications in health, sustainability, and biotechnology. While Genetic Design Automation (GDA) tools have optimized and streamlined the design of such circuits, rapid and efficient assembly of DNA remains a bottleneck in the Design-Build-Test-Learn (DBTL) cycle. Here, we present the Coli Toolkit (CTK), a modular Golden Gate-based cloning system, adapted from the Yeast Toolkit (YTK) for use in Escherichia coli. The CTK expands on the original YTK architecture by introducing a more flexible control of transcription and translation through subdividing the former promoter part into subparts: promoter, insulating ribozyme, and ribosome binding site (RBS). We provide a range of basic parts that enable the assembly of a wide range of constructs as well as characterization data for all constitutive and inducible promoters provided. Additionally, we provide characterization data, as well as calibrated models, for all 20 NOT gates from the Cello library, and we provide the NOT gates as preassembled basic parts, which enables rapid cloning of larger genetic circuits. With this toolkit, we leverage the strengths of the YTK architecture to enable rapid and high-efficiency assembly of genetic circuits in E. coli, filling a key gap in the infrastructure of bacterial synthetic biology.

Keywords:  MoClo; genetic design automation; golden gate; synthetic biology; toolkit

DOI:  https://doi.org/10.1021/acssynbio.5c00489
Nature. 2026 Jan 26.

Scalable and multiplexed recorders of gene regulation dynamics across weeks.

Lirong Zheng, Dongqing Shi, Yixiao Yan, Bingxin Zhou, Jormay Lim, Yongjie Hou, Bobae An, Jason K Adhinarta, Michael Lin, BumJin Ko, William C Joesten, Mehul Gautam, Elie D M Huez, Eung Chang Kim, Emily G Klyder, Boxuan Chang, Sethuramasundaram Pitchiaya, Michael T Roberts, Denise J Cai, Edward S Boyden, Donglai Wei, Pietro Liò, Changyang Linghu.

Gene expression is dynamically regulated by gene regulatory networks comprising multiple regulatory components to mediate cellular functions1. An ideal tool for analyzing these processes would track multiple-component dynamics with both spatiotemporal resolution and scalability within the same cells, a capability not yet achieved. Here, we present CytoTape, a genetically encoded, modular protein tape recorder for multiplexed and spatiotemporally scalable recording of gene regulation dynamics continuously for up to three weeks, physiologically compatible, with single-cell, minutes-scale resolution. CytoTape employs a flexible, thread-like, elongating intracellular protein self-assembly engineered via computationally assisted rational design, built on earlier XRI technology2. We demonstrated its utility across multiple mammalian cell types, achieving simultaneous recording of five transcription factor activities and gene transcriptional activities. CytoTape reveals that divergent transcriptional trajectories correlate with transcriptional history and signal integration, and that distinct immediate early genes (IEGs) exhibit complex temporal correlations within single cells. We further extended CytoTape into CytoTape-vivo for scalable, spatiotemporally resolved single-cell recording in the living brain, enabling simultaneous weeks-long recording of doxycycline- and IEG promoter-dependent gene expression histories across up to 14,123 neurons spanning multiple brain regions per mouse. Together, the CytoTape toolkit establishes a versatile platform for scalable and multiplexed analysis of cell physiological processes in vitro and in vivo.

DOI: https://doi.org/10.1038/s41586-026-10156-9
Adv Mater. 2026 Jan 27. e18755

Multiphysics-Driven Assembly of Biomimetic Vesicles.

Timofei Solodko, Ian Gimino, Aastha Chandiwala, Bayan Alkotoub, Ali Bashiri Dezfouli, Heiko Reith, Asjad Bakhtiar, Rojda Hicsanmaz, Johann Brenner, Christoph J O Kaiser, Elena Belli, Shilpi Pandey, Samuel D Rabkin, Kornelius Nielsch, Gabriele Multhoff, Oliver Hayden, Morteza Hasanzadeh Kafshgari.

  Artificial extracellular vesicles (AEVs) are programmable, biomimetic materials that combine the structural and biological complexity of naturally secreted extracellular vesicles (NEVs) with the design flexibility of synthetic nanomaterials. A multiphysics-driven microfluidics is developed to efficiently integrate the nanoknife-assisted membrane rupture with flow dynamics and acoustothermal modulation for the reproducible, high-yield, scalable, and standardized production of AEVs. Compared to empirical mechanical processes, this integrated microfluidic workflow, which exploits physical and biological insights for EV production, enables multiphysics-based predictions for a precise control of material inputs, flow dynamics, and cell-knife interactions within the channel. The biomimetic AEVs developed through this integrated, optimized single-flow platform, with a sustained and efficient therapeutic encapsulation process, preserve native protein architectures to conduct biomimetic mechanisms of immune modulation and homologous targeting. The standardizable microfluidic platform paves the way for a structure-process-function design strategy, enabling the formation of scalable, adaptive biomaterials for the development of bioinspired interfacial engineering and biomedicine.

Keywords:  cell membranes; extracellular vesicles; microfluidic platforms; multiphysics

DOI:  https://doi.org/10.1002/adma.202518755
JACS Au. 2026 Jan 26. 6(1): 3-26

Translating Nature's Design Rules: How Catalysis and Life Science Guide Molecular Catassembly.

Hang Qu, Fei Wang, Zhi-Chao Lei, Xin-Chang Wang, Liulin Yang, Xiao-Yu Cao, Chunhai Fan, Zhong-Qun Tian.

  Molecular assembly is a fundamental organizational principle in both living organisms and the fabrication of functional materials. However, artificial self-assembly systems lag far behind biological systems in terms of efficiency, controllability, complexity, and functionality. Here, inspired by catalysis in chemical reactions, we propose a novel strategy, termed as molecular catassembly, that employs catassemblers to dynamically manipulate cooperative multisite noncovalent interactions, thereby directing the pathway and accelerating assembly processes. By translating catalytic and biological principles into the catassembly, we summarize the distinctive features and multifaceted roles of catassemblers in manipulating cooperative multisite noncovalent interactions, facilitating mass transfer in crowded environments, and mediating energy transduction and feedback that endow systems with information-processing capabilities. Furthermore, we emphasize the pivotal role of catassemblers in multistep reaction-assembly cascades for the fabrication of hierarchical functional materials and the regulation of the cellular signaling pathway. We further elucidate how the integration of artificial intelligence technologies offers transformative potential to redefine the research paradigm of molecular (cat-)-assembly. Nevertheless, the research of catassembly remains in its infancy and demands the integration of advanced concepts and methodologies from multiple disciplines. Such interdisciplinary efforts will be crucial for unraveling the complexity and functionality of molecular assembly, ultimately offering new perspectives and methodologies for both life sciences and soft matter research.

Keywords:  catassembly; feedback; information systems; molecular assembly; nonequilibrium; reaction-assembly cascade

DOI:  https://doi.org/10.1021/jacsau.5c01001
Biomacromolecules. 2026 Jan 26.

Tyrosinase Cross-Linked PEG Hydrogels with DAT and DATT as Artificial Substrates: Design, Structure, and Functions.

Miroslava Racheva, Javier Basalo Lourido, Enise Ece Gurdal, Martin Herbst, Seyhmus Bayar, Daniela Radzik, Elen Bähr, Constanze Zwies, Axel T Neffe, Markus Pietzsch, Andreas Lendlein, Christian Wischke.

Enzymes such as oxidases are sustainable tools for hydrogel synthesis, but complex competing reactions have limited the mechanistic understanding and biomedical applications of these materials. Guided by molecular docking and MM-GBSA calculations, we identified two artificial substrates, desaminotyrosine (DAT) and desaminotyrosyltyrosine (DATT), that were experimentally more efficiently converted by mushroom tyrosinase (mTyr) than the natural substrate tyrosine. These substrates were used to synthesize hydrogels from DAT/DATT-functionalized star-shaped oligoethylene glycol (sOEG). Model reactions elucidated the chemical nature and functionality of the hydrogel netpoints. Material properties were systematically investigated depending on sOEG molecular weight (5, 10, 20 kDa), substrate type, and mTyr concentration. Functional mesh sizes and controlled release functions were investigated with fluorescent dextrans (4-500 kDa) and heparin. Cell culture studies with L929 fibroblasts and THP-1 monocytes suggested inertness of the material. These findings provide fundamental insight into mTyr-catalyzed hydrogel formation and support further exploration for in situ hydrogel synthesis.

DOI: https://doi.org/10.1021/acs.biomac.5c01929
Nature. 2026 Jan 28.

Optofluidic three-dimensional microfabrication and nanofabrication.

Xianglong Lyu, Wenhai Lei, Gaurav Gardi, Muhammad Turab Ali Khan, Shervin Bagheri, Mingchao Zhang, Metin Sitti.

Three-dimensional (3D) microfabrication/nanofabrication technologies have revolutionized various fields by enabling the precise construction of complex microstructures/nanostructures1-6. However, existing methods face challenges in fabricating intricate 3D architectures from a diverse range of materials beyond conventional polymers. Here we introduce a universal 3D microfabrication/nanofabrication strategy compatible with a broad range of materials by precisely manipulating optofluidic interactions within a confined 3D space, enabling the creation of volumetric, free-form 3D microstructures/nanostructures. A femtosecond-laser-induced heating spot generates a localized thermal gradient, providing precise spatiotemporal control over optofluidic interactions of the nanoparticle-laden dispersions. This enables the rapid and highly localized assembly of nanoparticles with diverse shapes and compositions-including metals, metal oxides, carbon nanomaterials and quantum dots-into complex 3D microstructures. To demonstrate its versatility, we fabricate multifunctional microdevices, such as 3D microfluidic valves with size-selective sieving functionality, achieving fast separation of microparticles/nanoparticles with distinct dimensions, as well as microrobots integrated with four distinct functional materials, achieving multimodal locomotion powered by different external stimuli. This optofluidic 3D microfabrication/nanofabrication method unlocks new opportunities for advanced material innovation and miniaturized device development, paving the way for broad applications in colloidal robotics7, microphotonics/nanophotonics, catalysis and microfluidics.

DOI: https://doi.org/10.1038/s41586-025-10033-x
ACS Appl Mater Interfaces. 2026 Jan 29.

One-Pot Strategy to Prepare Structurally Colored Alginate Dispersions for Functional Applications.

Ziqi Teng, Yaru Meng, Qinsheng Zhao, Yibo Zhao, Shuyuan Gao, Xinfu Pan, Shengjie Wang, Yongqing Xia.

  Structural colored hydrogels have emerged as a class of flexible optical materials with broad application prospects in smart color displays, wearable devices, sensors, and beyond. However, conventional preparation methods are often limited by time-consuming procedures and limited production scales. In this work, a structural colored sodium alginate (SA) dispersion was prepared by simply mixing an SA solution with an ultralow concentration of poly(styrene-methyl methacrylate-acrylic acid) colloidal emulsion and a small amount of cuttlefish ink. Depletion-induced interactions between the polymers drive the assembly of colloids into short-range ordered arrays within confined domains. When dominant scattering is suppressed, weak reflection signals become visible. Leveraging the ion-cross-linking capability of SA, the structural colored dispersion can be solidified via rapid gelation with CaCl2 or through a mild treatment using slow-releasing Ca2+ sources. As a result, the structural colored SA dispersion can serve as a functional ink for fabricating fibers and hydrogels through various solution-based processing techniques such as wet spinning, coaxial printing, dip coating, and extrusion-based 3D printing. This study demonstrates that the one-pot preparation of structural colored polymer dispersions offers a versatile and promising platform for diverse applications.

Keywords:  alginate hydrogel; coaxial printing; direct ink writing; fibers; structural colored dispersion

DOI:  https://doi.org/10.1021/acsami.5c23869
Adv Mater. 2026 Jan 28. e19226

Bioinspired Programmable Biaxial Rolling Gel Sheets for Complex 3D Morphing.

Yinmin Cai, Changxian Wang, Man Yang, Yuepeng Li, Feilong Zhang, Shutao Wang.

  Shape-morphing gels have shown promising applications in widespread fields, including soft robotics, flexible electronics, and smart medicine. The majority of efforts have been focused on rapid response and multi-responsiveness of shape-morphing materials with bilayer structure. However, achieving biaxial rolling with controllable curvature remains a critical challenge. Herein, inspired by the hygroscopic heterostructures in pine cone scale, we report a sinusoidal-patterned hydrogel-semi-embedded-organogel (HSEO) sheet constructed by wetting-enabled 3D interfacial polymerization (WET-DIP) strategy. The sinusoidal pattern serves as a programmable geometric template to redistribute anisotropic stress spatially. By tuning sinusoidal pattern parameters, we realize biaxial morphing and the modulation of longitudinal and transversal curvatures, consistent with the results of finite element analysis (FEA). The semi-embedded heterostructure offers compressive force on the organogel to overcome isotropic stress limitations. Notably, this design leverages the sinusoidal periodic topology and semi-embedded structure to precisely modulate stress distribution, enabling counterintuitive rolling behaviors and complex 3D transformations. This work pioneers a counterintuitive and programmable shape-morphing mechanism for complex 3D architectures, offering a perspective for novel soft actuators.

Keywords:  biaxial rolling; bioinspired; gel; programmable shape morphing

DOI:  https://doi.org/10.1002/adma.202519226
Science. 2026 Jan 29. 391(6784): 446-447

Controlling plastic behavior with light.

Jake L Nicholson, Quentin Michaudel.

Thermoplastic properties are spatially tuned with light intensity during three-dimensional (3D) printing.

DOI: https://doi.org/10.1126/science.aee7263
Biomacromolecules. 2026 Jan 27.

Protein-Delivering Polyelectrolyte Complex Hydrogels: Structure, Swelling and Dissolution Characteristics, and Release Behavior.

Holly Senebandith, Khin C Pyone, Marlo O Taylor, Fahed Albreiki, Maanasi H Dhiraj, Samanvaya Srivastava.

We demonstrate triblock polyelectrolyte complex (PEC) hydrogels as a model platform for protein delivery and unveil their precisely tunable swelling behaviors. PEC hydrogels self-assemble in water, do not require UV light or organic solvents, and demonstrate easily tunable shear properties. However, for PEC hydrogels to be effectively designed as protein delivery vehicles, it is imperative to understand the influence of protein additives on their microstructure and swelling behavior. Herein, we utilize small-angle X-ray scattering to demonstrate that model proteins, including bovine serum albumin, lipase, human carbonic anhydrase II, and urease, do not perturb the PEC hydrogel microstructure at therapeutically relevant concentrations. The swelling and dissolution characteristics are shown to be precisely controlled by triblock polyelectrolyte (tbPE) end-block length and concentration. Moreover, we demonstrate that PEC hydrogel swelling and dissolution characteristics, as well as their shear moduli, are unaffected by protein inclusion. Finally, we demonstrate tunable protein release in PEC hydrogels by varying tbPE concentration and end-block length, mixing tbPEs of different lengths to create mixed PEC hydrogels, and incorporating a covalent interpenetrated network. Our work provides easily accessible design parameters to achieve the desired protein release characteristics in PEC hydrogels. At the same time, it also provides insights into the influence of charged macromolecules on the microstructure and dynamics of PEC-based self-assemblies.

DOI: https://doi.org/10.1021/acs.biomac.5c02347
bioRxiv. 2026 Jan 10. pii: 2022.08.15.503769. [Epub ahead of print]

Deriving genetic codes for molecular phenotypes from first principles.

Salil S Bhate, Anna Seigal, Juan Caicedo.

The genetic code is a formal principle that determines which proteins an organism can produce from only its genome sequence, without mechanistic modeling. Whether similar formal principles govern the relationship between genome sequence and phenotype across scales - from molecules to cells to tissues - is unknown. Here, we show that a single formal principle - structural correspondence - underlies the relationship between phenotype and genome sequence across scales. We represent phenotypes and the genome as graphs and find mappings between them using structure preservation as the sole constraint. Combinatorial richness in phenotypes more tightly constrains which mappings preserve that structure. Thus, phenotypic structure predicts genetic associations independently of covariation with genotype. This principle rediscovers the amino acid code without prior knowledge of translation or coding sequences, using just one protein and genome sequence as input. We benchmark this principle: applied to phenotypes at the cell, tissue and organ scales, the mappings correctly predict established associations and are driven by transcription factor motifs. Applied to cancer tissue images, we find regulators of spatial gene expression in immune cells. We thus offer a first-principles framework to relate genome sequence with phenotypic structure and guide mechanistic discovery across scales.

DOI: https://doi.org/10.1101/2022.08.15.503769
Small. 2026 Jan 29. e14890

Bioinspired Ultratough and Rapidly Responsive Hydrogels Empower Silent Communication.

Shuaibo Zhang, Donglei Fu, Junjie Deng, Ruyi Wei, Xinghai Liu.

  The development of sustainable flexible electronics is hindered by a lack of sensing materials that synergize eco-friendliness, robust mechanical properties, and reliable electromechanical responsiveness. While starch-based hydrogels present a promising sustainable alternative, their widespread application is limited by inherent brittleness and significant signal hysteresis. Here, a molecular engineering strategy is proposed to address these limitations. Porous starch is first obtained through a gradual solvent exchange process to enhance chain accessibility. Protocatechuic acid (PCA) is then covalently grafted onto the starch backbone via EDC/NHS-mediated esterification, introducing dynamic hydrogen-bonding and π - π interaction motifs. By optimizing the ratio between PCA-modified starch and polyacrylamide (PAM), a bioinspired hydrogel with exceptional toughness and rapid electromechanical response is achieved. The resultant hydrogel exhibited pronounced strain-dependent resistance behavior, enabling its integration into a wireless wearable human-machine interface. To ensure robust decoding against motion-induced noise, a finite state machine (FSM)-based algorithm is employed for adaptive signal segmentation, achieving a character-level accuracy of 99.2% in trials with healthy subjects (n = 10). This work not only introduces a high-performance, sustainable hydrogel platform but also demonstrates a practical route toward inclusive and language-independent human-machine communication.

Keywords:  catechol functionalization; finite state machine; piezoresistive sensing; starch‐based hydrogel; wearable electronics

DOI:  https://doi.org/10.1002/smll.202514890
ACS Appl Mater Interfaces. 2026 Jan 27.

Development of Organogel-AFPT System for Encapsulation and Cryopreservation of Yarrowia lipolytica.

Ziying Zhang, Ruiqi Cui, Haoyu Yang, Xiangyu Zhang, Lei Zhang.

  Encapsulation of microorganisms is a promising strategy in biomedical and industrial applications to enhance stability, reusability, and functionality. However, the cryopreservation of microorganism-encapsulated materials still represents a formidable challenge because of the mechanical and osmotic damage caused by inevitable ice formation at subzero temperatures. In this study, we developed a hydrophobic antifreeze material (organogel-AFPT) specifically for oleaginous microorganisms, following the principle of reducing the overall water content of the system and inhibiting ice nucleation and growth. By the cryoprotection of organogel-AFPT, 94% survival rate of Yarrowia lipolytica (Y. lipolytica) can be achieved after cryopreservation at -196 °C. It is also found that the organogel-AFPT can serve as a convenient platform for information encryption and decryption. The findings in this work provide a new strategy for the development of antifreeze living materials.

Keywords:  Yarrowia lipolytica; antifreeze peptides; cryopreservation; encapsulation; organogel

DOI:  https://doi.org/10.1021/acsami.5c22113
Proc Natl Acad Sci U S A. 2026 Feb 03. 123(5): e2528600123

Friction-controlled reentrant aging and fluidization in granular materials.

Ye Yuan, Walter Kob, Hajime Tanaka.

  Granular materials densify under repeated mechanical perturbations, nonequilibrium dynamics that underlies many natural and industrial processes. Because granular relaxation is governed by frictional contacts and energy dissipation, this aging behavior fundamentally differs from that of thermal glasses despite their apparent similarities. Here, we uncover how friction controls the compaction dynamics of granular packings subjected to quasistatic cyclic shear. Using discrete element simulations, we construct a dynamic state diagram as a function of strain amplitude and friction, revealing a rich interplay among jamming marginality, stabilization, and fluidization. We identify a friction-dependent crossover strain that separates aging and fluidized regimes, showing reentrant, nonmonotonic behavior: Increasing friction first suppresses fluidization but then promotes it through smooth, creep-like rearrangements. This transition is marked by a shift from intermittent, avalanche-like rearrangements to continuous, diffusive motion. Our findings demonstrate that friction exerts a dual role in granular aging-both stabilizing and fluidizing-thereby uncovering the fundamental nonequilibrium mechanisms that govern compaction, rheology, and aging in athermal disordered systems. More broadly, our results reveal a general principle for how friction governs metastability and flow in athermal matter-from granular and frictional colloids to soils and seismic faults-linking microscopic contact mechanics to macroscopic dynamics.

Keywords:  compaction and aging; frictional dynamics; granular materials; jamming and fluidization

DOI:  https://doi.org/10.1073/pnas.2528600123
Nano Lett. 2026 Jan 26.

van der Waals Nanochemical Reactors.

Zhaoyi Joy Zheng, Haosen Guan, Danrui Ni, Guangming Cheng, Yanyu Jia, Ipsita Das, Yue Tang, Ayelet J Uzan-Narovlansky, Lihan Shi, Kenji Watanabe, Takashi Taniguchi, Nan Yao, Robert J Cava, Sanfeng Wu.

  Synthesizing single crystals suitable for quantum electronic discoveries remains challenging for many emerging materials. We introduce van der Waals (vdW) stacks as nanochemical reactors for single-crystal synthesis and demonstrate their broad applicability in growing both elemental and compound crystals at the micrometer scale. By encapsulating atomically thin reactants that are stacked compactly with inert vdW layers, we achieve nanoconfined synthesis with the resulting crystals remaining encapsulated. As a proof of concept, we synthesized isolated single crystals of elemental tellurium and distinct types of Pd-Te compounds. Structural characterization confirms the high crystalline quality of the products. We observe the intrinsic semiconducting gap of tellurium and superconductivity in nonstoichiometric PdTe1-x with a significantly reduced Te content. The concept of vdW nanoreactors is broadly generalizable, chip-integrable, well-suited to a wide range of processing conditions, and compatible with nanofabrication, offering a versatile pathway to expand the accessible landscape of quantum materials.

Keywords:  nanoreactors; synthesis; van der Waals materials

DOI:  https://doi.org/10.1021/acs.nanolett.5c06176
Proc Natl Acad Sci U S A. 2026 Feb 03. 123(5): e2529200123

Behavioral tuning of spider silk thread stiffness circumvents biomaterial trade-offs.

Jonas O Wolff, Daniela C Rößler, Anna-Christin Joel, Vincent Jackel, Sebastian Büsse, Peter Michalik, Martín J Ramírez.

  Biological polymers often face a trade-off between stiffness, strength, and extensibility: Materials that are strong and stiff tend to be brittle, while those that are elastic and extensible usually lack strength. Here, we show that netcasting spiders (Deinopidae) overcome this trade-off by forming mixed-silk metastructures, which enable both high elastic deformation and load resistance. These spiders have evolved a unique predatory strategy, casting a sticky silk web over prey, which subjects the web radii to extreme strains far exceeding those sustained by typical spider silk fibers. The radii consist of a compound filament with an elastomeric core surrounded by looped bundles of thin fibers. This architecture results in an unusual mechanical profile: The threads are initially compliant and highly extensible, but they stiffen as the fiber loops straighten, enhancing load-bearing capacity. Notably, spiders control this compound architecture through a reel-spinning technique, controlling loop formation and fiber mixture to establish an elasticity gradient across the web-stiff and strong in the main frame lines, yet soft and hyperelastic in the lower radii that undergo the greatest deformation during prey capture. These findings represent a unique case of behavioral modulation of silk processing to circumvent biomaterial trade-offs, enabling extraordinary dynamics and specialization of web architecture. The herein described principle of looped fiber-reinforced elastomers may also be transferred to the design of artificial materials for applications that require both high elasticity and strength.

Keywords:  adaptive material; hybrid material; mechanical trade-off; metastructure; spider web

DOI:  https://doi.org/10.1073/pnas.2529200123
ACS Macro Lett. 2026 Jan 27.

PEGylated DNA Helper Molecule-Assisted Self-Assembly of Polyelectrolyte Complex Micelles.

Kwanghee Lee, Jin Sol Shin, Weijia Tang, Jeehae Shin, Sheng Li.

Polyelectrolyte complex micelles (PCMs) offer a promising platform for oligonucleotide delivery; however, conventional preparation methods based on block copolymers require chemical modification of either the oligonucleotide cargo or the cationic carrier polymer. Here, we report a modified strategy for PCM formation in which the ends of target DNAs (tDNAs) are hybridized with poly(ethylene glycol)-conjugated DNA (DNA-PEG) helper molecules to generate diblock and triblock pseudoblock copolymers (pseudo-BCPs). These pseudo-BCPs are subsequently complexed with branched polyethylenimine (BPEI) to form PCMs. Pseudo-BCPs bearing PEG chains of 5 kg/mol (pseudo-BCP(5k)) or greater yield PCMs with well-defined core-shell morphologies and exhibit excellent temporal stability and salt resistance. In vitro analyses using cultured cells demonstrate that all PCM systems show enhanced cellular uptake relative to free tDNA, with pseudo-BCP(5k)-derived PCMs exhibiting the highest efficiency. These results establish pseudo-BCP-based PCM assembly as a feasible new route to prepare nanocarriers for oligonucleotide delivery.

DOI: https://doi.org/10.1021/acsmacrolett.5c00779
Proc Natl Acad Sci U S A. 2026 Feb 03. 123(5): e2532504123

Coordination of cell organelles to promote metabolon formation.

Zhou Sha, Anthony M Pedley, Timothy D Iles, Shaoqing Zhang, Jack R Staub, Ruobo Zhou, Stephen J Benkovic.

  The spatial coordination between cellular organelles and metabolic enzyme assemblies represents a fundamental mechanism for maintaining metabolic efficiency under stress. While previous work has shown that membrane-bound organelles regulate metabolic activities and that membrane-less condensates conduct metabolic reactions, the coordination between these two organizations remains unaddressed. By using a combination of proximity labeling, superresolution fluorescence microscopy, and metabolite analyses using isotopic tracing, we investigated the relationships between these metabolic hotspots. Here, we show that nutrient deficiency elongates mitochondria and transforms the ER from a tubular to sheet-like morphology, coinciding with increased mitochondrial respiration and inosine 5'-monophosphate levels. These structural changes promote the colocalization of purinosomes with these organelles, enhancing metabolic channeling. Disruption of ER sheet formation via MTM1 knockout destabilizes purinosomes, impairs substrate channeling, and reduces intracellular purine nucleotide pools without altering enzyme expression. Our findings reveal that organelle morphology and interorganelle contacts dynamically regulate the assembly and function of metabolic condensates, providing a structural basis for coordinated metabolic control in response to nutrient availability.

Keywords:  biomolecular condensates; cell metabolism; de novo purine biosynthesis; metabolon; purine

DOI:  https://doi.org/10.1073/pnas.2532504123
Nat Commun. 2026 Jan 28.

Lipid Nanoparticle Database towards structure-function modeling and data-driven design for nucleic acid delivery.

Evan Collins, Jungyong Ji, Sung-Gwang Kim, Jacob Witten, Seonghoon Kim, Richard Zhu, Peter Park, Minjun Jung, Aron Park, Rajith S Manan, Arnab Rudra, Gyochang Keum, Eun-Kyoung Bang, Jun-O Jin, William J Jeang, Robert Langer, Daniel G Anderson, Wonpil Im.

Lipid nanoparticles (LNPs) are the leading nonviral nucleic acid delivery technology, but LNP structure-function data remains fragmented and nonstandardized. Unlike protein engineering which is anchored by the centralized Protein Data Bank, the LNP field lacks a unified repository for systematic analysis. To address this, we develop Lipid Nanoparticle Database (LNPDB) (https://lnpdb.molcube.com), an integrated database and web tool that consolidates structural and functional data for 19,528 LNPs. LNPDB standardizes LNP featurization by encoding lipid composition, experimental methods, and functional results, and generates CHARMM force field files for constituent lipids to enable molecular dynamics simulations. LNPDB also supports future data contributions for continued growth. We examine the utility of LNPDB through two applications: advancing our deep learning model for predicting LNP delivery performance, and simulating bilayer dynamics to identify structural features - bilayer stability and critical packing parameter - that correlate with LNP delivery performance. Altogether, LNPDB provides the digital framework for LNP modeling and data-driven rational design.

DOI: https://doi.org/10.1038/s41467-026-68818-1