bims-enlima 2026-03-01 papers

bims-enlima

Biomed News

on Engineered living materials

Issue of 2026–03–01
28 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool

Ultrafast-relaxing and photopolymerizable PEG hydrogels enable viscoelasticity-mediated cell remodeling in synthetic matrices.
Designing Self-Healing, Printable, and Tough Conductive Hydrogels via the Synergy of Orthogonal Photochemistry and Hofmeister Effect.
Microbial Polymers and Living Interfaces: Interplay Between Matter and Microbes.
Topological control of spontaneous failure in active nematic solids.
Light-induced assembly and repeatable actuation in Ca2+-driven chemomechanical protein networks.
Soft photo-ionotronics.
Conformation-driven mechanical duality: Viscoelastic and poroelastic switching in protein hydrogels.
Formation of a swelling gel underlies a morphological transition in Bacillus subtilis biofilms.
An information theory approach to quantifying the sequence-dependent response of nucleic acid motors with applications to nanopore DNA sequencing.
Bioactive and Injectable Granular Hydrogels Incorporating Decellularized Extracellular Matrix.
Robust Hydrogel Lubricating Modification of High-Modulus Polymer Surfaces via Structure-Based Stress Transfer and Chain Interpenetrating Anchoring.
Engineered Protein-Cellulose Composite Hydrogels with Superior Mechanical Performance for Bioadhesion.
3D Bioprinting of Continuous Nanofibrous Yarn-Reinforced Cell-Laden Constructs.
Programmable and Switchable RNA Scaffolds for Synthetic Condensate Engineering in Mammalian Cells.
Hierarchical Logic Control via DNA Polymerase-Driven Molecular Circuits.
Engineering non-exponential proliferation in Escherichia coli using functionalized protein aggregates.
Building like a Coral-Parallelized, Multiscale Biofabrication.
Mechanically and Functionally Resilient Piezoelectric Fiber Coils and Knots for Reliable Self-Powered Sensing.
Bottlebrush Polymers for Multiphoton 3D Laser Printing.
Highly mutagenic continuous evolution in E. coli using a Φ29-based orthogonal replication system.
From peptides to DNA: All required steps can be catalyzed.
Rational design of synthetic proteins using a genome-scale CRISPR screen.
The Impact of Fungal Developmental Structures on Mechanical Properties of Mycelial Materials.
Tensile expansion microscopy applies mechanical force to super-resolve fixed and image live cellular samples.
Proteoliposomes containing ATPase as microreactors to mimic microbial metabolism for bioenergy synthesis.
DNA Framework-Encoded Digital Recorder for Bacterial Discrimination.
Compliant and Tough Triboelectric-Piezoresistive Porous Hydrogels Enabled by Interfacial Assembly of Nanocellulose Microgels.
A Versatile Zwitterionic Gelation Strategy Triggered by Phenol-Modified Biomacromolecules: Facile Synthesis of Bioactive and Customizable Hydrogels.

Matter. 2026 Feb 04. pii: 102524. [Epub ahead of print]9(2):

Ultrafast-relaxing and photopolymerizable PEG hydrogels enable viscoelasticity-mediated cell remodeling in synthetic matrices.

Bruce E Kirkpatrick, Abhishek P Dhand, Lea Pearl Hibbard, Matthew W Jaeschke, Tvishi Yendamuri, Benjamin R Nelson, Joshua S Lee, Kaustav Bera, Hannah M Zlotnick, Carly A Fox, Bianca Meurer-Zeman, Connor E Miksch, Nathaniel P Skillin, Michael R Blatchley, Timothy J White, Christopher N Bowman, Jason A Burdick, Kristi S Anseth.

  Synthetic hydrogels provide powerful material platforms to engineer cellular microenvironments with control over stiffness, viscoelasticity, porosity, degradability, and biochemical signals. Here, we demonstrate how orthogonal crosslinking reactions allow fabrication of covalent adaptable networks to tailor photopolymerizable bioresin formulations relevant for tissue engineering. Specifically, we synthesize multifunctional poly(ethylene glycol) (PEG) macromers containing dynamic boronate ester bonds and dithiolane and norbornene moieties that allow for photopolymerization and projection-based biofabrication. These materials are used to print human mesenchymal stromal cells (MSCs) in formulations where the ratio of elastic versus adaptable crosslinks is engineered to study and manipulate MSC spreading, actin structure, and macroscopic material-level deformation. We demonstrate how material and print parameters, peptide ligands, actomyosin-modulating drug treatments, and cell types influence cell-material interactions and emergence of morphogenesis that is uniquely enabled by viscoelasticity. The presented materials introduce a versatile strategy for spatiotemporal control over dynamic mechanical properties in cell-laden matrices.

Keywords:  PEG hydrogel; boronate ester; dithiolane; hMSC; photopolymerization; viscoelasticity

DOI:  https://doi.org/10.1016/j.matt.2025.102524
Macromol Rapid Commun. 2026 Feb 27. e00005

Designing Self-Healing, Printable, and Tough Conductive Hydrogels via the Synergy of Orthogonal Photochemistry and Hofmeister Effect.

Mingjie Hu, Qian Wang, Yuchan Huang, Zhe Lu, You Yu.

  Developing conductive hydrogels that combine high toughness, self-healing capabilities, and 3D printing performance is crucial for flexible electronics, but it remains a significant challenge due to the inherent performance trade-offs of traditional manufacturing methods. Herein, we present a synergy of orthogonal photochemistry and Hofmeister effect strategy for the rapid fabrication of high-performance conductive hydrogels. Under visible light, ruthenium photochemistry triggers three orthogonal reactions comprising the radical polymerization of poly(vinyl alcohol acetoacetate), the oxidative polymerization of ethylenedioxythiophene, and the phenol coupling of gelatins within seconds. A subsequent Hofmeister effect-mediated post-treatment induces hierarchical polymer crystallization to endow the hydrogels with exceptional toughness of 3.1 MJ m-3 and fatigue resistance. Furthermore, the dynamic hydrogen-bonding network and gelatin grant the hydrogel a rapid self-healing efficiency of approximately 90%. The resulting hydrogels are fully compatible with extrusion-based 3D printing to enable the fabrication of customizable and self-healing resistive and capacitive sensors capable of reliable motion monitoring. This work establishes a versatile and efficient platform for engineering multifunctional soft materials for wearable devices.

Keywords:  3D printing; conductive hydrogels; orthogonal photochemistry; self‐healing; tough hydrogels

DOI:  https://doi.org/10.1002/marc.202600005
Annu Rev Chem Biomol Eng. 2026 Feb 27.

Microbial Polymers and Living Interfaces: Interplay Between Matter and Microbes.

Julia Amorim, Patrice Crosby, Jennifer Tran, Wren Kitchings, Rong Yang, Eleftheria Roumeli.

Polymer design is being reshaped by demands for low-carbon fabrication and bioactive/living function. We trace the bidirectional interface between microbes and polymers. First, we analyze how microbes synthesize polymers like polysaccharides, polyesters, and proteins and how post-synthesis processing (via mechanical and/or chemical treatments) reshapes molecular architecture and mechanical and thermal properties. We compare reported properties, highlight missing metrics, and evaluate sustainability levers including solvent recovery, cradle-to-gate impacts, and biodegradation/biocontainment constraints. Second, we examine how polymers shape the behavior of living organisms in the context of engineered living materials. Design is organized around four axes-regulating adhesion and detachment, sustaining or directing growth for regeneration, imposing spatial organization on consortia, and tuning phenotype-with implementations in drug delivery, carbon capture, antimicrobial screening, and structural composites. Finally, we outline how automation, artificial intelligence-guided experimentation, and robust sustainability metrics can couple performance with responsible deployment.

DOI: https://doi.org/10.1146/annurev-chembioeng-100724-081311
Nat Mater. 2026 Feb 25.

Topological control of spontaneous failure in active nematic solids.

Sheng Chen, Matthew Ricci, A Pasha Tabatabai, Zachary Gao Sun, Sven Witthaus, Suraj Shankar, Mor Nitzan, Michael P Murrell.

Active solids using energy influx to generate non-equilibrium forces undergo spontaneous mechanical failure, but how topological defects concentrate internal stresses and control breakage in active materials is unknown. Here we assemble a reconstituted two-dimensional actomyosin network that lacks fluidity but exhibits nematic order and network elasticity. Surprisingly, we found that interacting multidefect configurations, especially defect quadrupoles with two +1/2 and two -1/2 defects, play a crucial role. Combining experimental data with an active solid fracture model, we demonstrate that a head quadrupole with mutually facing +1/2 defects can trigger crack opening and material tearing. Meanwhile, tail quadrupoles with mutually opposing +1/2 defects drive transient filament clustering and condenses into asters. We establish a deep learning model to predict the eventual aster formation from the initial topological structures. Our work uncovers a defect-mediated mechanism for spontaneous failure in active solids and provides topological design principles for controlling targeted damage in soft and living systems across scales.

DOI: https://doi.org/10.1038/s41563-026-02493-x
Nat Commun. 2026 Feb 21.

Light-induced assembly and repeatable actuation in Ca2+-driven chemomechanical protein networks.

Xiangting Lei, Carlos Floyd, Laura Casas-Ferrer, Tuhin Chakrabortty, Nithesh Chandrasekharan, Aaron R Dinner, Scott Coyle, Jerry Honts, Saad Bhamla.

Programming rapid, repeatable motions in soft materials has remained a challenge in active matter and biomimetic design. Here, we present a light-controlled chemomechanical network based on Tetrahymena thermophila calcium-binding protein 2 (Tcb2), a Ca2+-sensitive contractile protein. These networks-driven by Ca2+-triggered structural rearrangements-exhibit dynamic self-assembly, spatiotemporal growth, and contraction rates comparable to actomyosin systems. By coupling light-sensitive chelators for optically triggered Ca2+ release, we achieve precise growth and repeatable mechanical contractility of Tcb2 networks, revealing emergent phenomena such as boundary-localized active regions and density gradient-driven reversals in motion. A coupled reaction-diffusion and elastic model explains these dynamics, highlighting the interplay between chemical network assembly and mechanical response. We further demonstrate active transport of particles via network-mediated forces in vitro and implement reinforcement learning to program seconds-scale spatiotemporal actuation in silico. These results establish a platform for designing responsive active materials with rapid chemomechanical dynamics and tunable optical control, with applications in synthetic cells, sub-cellular force generation, and programmable biomaterials.

DOI: https://doi.org/10.1038/s41467-026-69651-2
Nat Commun. 2026 Feb 21.

Soft photo-ionotronics.

Xu Liu, Steven M Adelmund, Shahriar Safaee, Wenyang Pan, Thomas J Wallin.

The ability to control the movement of charged species in the circuitry of living beings and machines is essential for complex signal processing, computation, and, ultimately, higher functionality. We describe a class of photo-ion generators (PIGs) based on non-ionic photoacids that can create large (> 1000x) irreversible changes in ionic conductivity under illumination, depending on the PIG species, concentration, and solvent. Incorporation of PIGs into elastomers by simple swelling methods yields soft (60 kPa ≤ E ≤ 10 MPa), stretchable, photo-ionic gels (PIGels). The resolution of photo-patterned conductivity in PIGels is less than 1 cm and demonstrates stability over several days, suggesting utility in engineered devices. Leveraging the photo-responsive properties of these materials, we demonstrate high-sensitivity mechanical sensors via conductance changes ([∆G/G0]/σ = 20 MPa-1) and photo-writable, soft circuitry.

DOI: https://doi.org/10.1038/s41467-026-69427-8
Acta Biomater. 2026 Feb 20. pii: S1742-7061(26)00122-4. [Epub ahead of print]

Conformation-driven mechanical duality: Viscoelastic and poroelastic switching in protein hydrogels.

Mattan Ze'ev Becker, Maya Georgia Pelah, Ofek Avrahami, Ionel Popa, Ronen Berkovich.

  Bovine serum albumin (BSA) hydrogels reveal a fundamental mechanical duality in protein-based biomaterials. Using chemically crosslinked BSA networks as a model system, we show that the same hydrogel can dissipate stress through two distinct regimes depending on protein conformation. Native BSA hydrogels exhibit viscoelastic relaxation, governed by unfolding of protein domains, whereas chemically denatured BSA hydrogels display poroelastic dissipation, dominated by solvent migration through the deformed matrix. This denaturation-driven switch between viscoelastic and poroelastic mechanics highlights the direct coupling between protein structure and macroscopic energy dissipation. By disentangling these two dissipative modes within a single material platform, our findings provide a conceptual framework for designing protein-based hydrogels with state-dependent mechanical responses, with potential applications in biomaterials, mechanobiology, and soft matter engineering. STATEMENT OF SIGNIFICANCE: This study reveals how the folding state of proteins controls the way protein-based hydrogels dissipate mechanical energy. We show that native proteins give rise to viscoelastic behavior, while denatured proteins display poroelasticity, and, most notably, that these two regimes can reversibly switch within the same material. This discovery introduces a new concept of dynamically tunable soft materials, advancing biomaterial design beyond static systems. Our work combines mechanical testing, molecular-level insights, and machine learning-based analysis to connect protein structure with hydrogel mechanics across length scales. These findings open new pathways for designing smart biomaterials with applications in tissue engineering and related biomedical technologies.

Keywords:  Bovine serum albumin; Hydrogel; Poroelasticity; Protein unfolding; Protein-based biomaterials; Viscoelasticity

DOI:  https://doi.org/10.1016/j.actbio.2026.02.038
bioRxiv. 2026 Feb 22. pii: 2026.02.20.707077. [Epub ahead of print]

Formation of a swelling gel underlies a morphological transition in Bacillus subtilis biofilms.

Ayantika Saha, Joshua M Jones, Abigail Plummer, Joseph W Larkin.

Microbes across species and environments form biofilms, living materials composed of cells and extracellular polymers. Biofilm-dwelling cells benefit from emergent soft matter physics that sculpts three-dimensional morphologies and osmotically absorbs nutrients. Although biofilms are modeled as viscoelastic gels, the physical origins of the phase transition underlying their conversion from groups of cells to living gels have not been systematically investigated. Here, we show that Bacillus subtilis biofilms use polymer composition to tune their physical properties and drive gel formation. Using imaging and water immersion experiments with matrix knockout strains, we demonstrate the complementary roles of two polymers in this developmental transition: hydrophilic poly- γ -glutamate swells colonies by absorbing water and exopolysaccharides serve as effective cross-linkers, causing a sol-gel-like phase transition that imparts structural integrity. With matrix knockout co-culture biofilms, we independently modulate the production of each polymer and reveal a phase space of biofilm morphologies. Colonies that produce both polymers develop macroscopic wrinkles. A thin-film model predicts biofilm wrinkling from swelling-generated internal strain coupled to elasticity. The model reproduces the shape of our observed morphological phase diagram. Our results demonstrate that bacteria leverage gelation to vary their material properties and morphologies, with implications for microbial ecology and engineering living matter.

DOI: https://doi.org/10.64898/2026.02.20.707077
Nat Commun. 2026 Feb 26.

An information theory approach to quantifying the sequence-dependent response of nucleic acid motors with applications to nanopore DNA sequencing.

Jonathan M Craig, Andrew H Laszlo, Henry Brinkerhoff, Christopher A Thomas, Sinduja K Marx, Eric F Lebo, Sarah J Abell, Michaela C Franzi, Jesse R Huang, Hwanhee C Kim, Jessica D Carrasco, Jens H Gundlach.

Motor enzymes that interact with DNA are essential for replicative biological processes. In nanopore sequencing, a motor enzyme controls the motion of a nucleic acid through a protein nanopore, and sequence-dependent blockages of an ion current flowing through the nanopore are used to decode the DNA sequence. The kinetics of these enzymes are sequence-dependent and can serve as an additional source of information during sequencing. Here, we use Mutual Information (MI) to quantify the sequence-dependent kinetics of a Hel308 helicase during nanopore sequencing. We use MI to identify sites in Hel308 that are responsible for sequence-dependent kinetics and develop "k-mer" models of Hel308 kinetics that map kinetics to DNA sequence. We estimate that enzyme kinetics can improve nanopore sequencing accuracy by ~5-fold at high sequencing depth. We mutate Hel308 to identify amino acids involved in DNA translocation and suggest pathways for engineering molecular motors with enhanced responsiveness to DNA sequence.

DOI: https://doi.org/10.1038/s41467-026-69867-2
ACS Biomater Sci Eng. 2026 Feb 23.

Bioactive and Injectable Granular Hydrogels Incorporating Decellularized Extracellular Matrix.

Daniela Trindade, Nikolas Di Caprio, Ana C Maurício, Nuno Alves, Carla Moura, Jason A Burdick.

  Decellularized extracellular matrices (dECMs) provide bioactive cues that may be useful for the repair of fibrocartilaginous tissues, such as the temporomandibular joint disc (TMJd), which lacks a natural regenerative capacity. While potent in bioactivity, dECM hydrogels do not possess the mechanical properties necessary for joint repair, motivating the development of improved materials. Granular hydrogels provide a unique opportunity to repair tissues by mechanically stabilizing the defect with injectable, jammed hydrogel microparticles that exhibit microporosity to support cellular infiltration. Here, we combined the bioactivity of dECM with the stability of norbornene hyaluronic acid (NorHA) granular hydrogels to create a system that promotes cell adhesion and allows for ECM release. Two concentrations of dECM (0.4% and 0.8%, w/v, dry weight) were encapsulated within NorHA microgels and shown to increase microgel stiffness and support ECM release over time. The microgels were formed into granular hydrogels with shear-thinning and self-healing properties that also undergo secondary cross-linking either with photo-cross-linking via visible light or with the addition of an interstitial dECM. The incorporated dECM supported the adhesion of fibrochondrocytes. The addition of dECM to microgels and within the interstitial space resulted in an injectable and bioactive biomaterial.

Keywords:  decellularized extracellular matrix; granular hydrogels; hyaluronic acid; injectable; temporomandibular joint

DOI:  https://doi.org/10.1021/acsbiomaterials.5c02060
Small. 2026 Feb 27. e14771

Robust Hydrogel Lubricating Modification of High-Modulus Polymer Surfaces via Structure-Based Stress Transfer and Chain Interpenetrating Anchoring.

Zhaofei Ma, Zhikun Wang, Jingyue Wang, Zhencai Xing, Weihe Wang, Guorui Zhang, Bo Yu, Xiaowei Pei, Yanfei Ma, Chenxi Qin, Songqing Hu, Feng Zhou.

  Hydrogel lubrication modification of hard polymer surfaces shows broad application prospects in soft robotics, tissue engineering, and biomedical devices. However, orders-of-magnitude differences in modulus can easily lead to stress concentrations at the interface between soft and hard materials, increasing material failure, especially in the field of artificial joint replacement, which involves high-load service. Herein, we propose a robust hydrogel lubricating modification strategy for high-modulus polymer surfaces via gradient-structured stress-transfer dissipation and interfacial polymer chain interpenetrating anchoring. The material modulus of the entire lubrication system increases sequentially from the outside in-the modulus of the hydrogel portion increases by more than two orders of magnitude, from hundreds of kilopascals to megapascals, and then to 10 megapascals, at which point the hydrogel modulus matches the high-modulus polymer (polydimethylsiloxane). The surface of the high-modulus polymer and the hydrogel are anchored together through the interpenetration of polymer chains (anchoring force of 250 N·m-1). What's more, this nonhomogeneous surface structure construction achieves high load-bearing and ultra-low friction simultaneously, which are inherently in conflict, with one raised at the expense of the other. This unique approach provides the high-modulus polymer surface with robust lubricating capacity with a low coefficient of friction (COF: ∼0.03) and maintains stable lubricity under ultimate-load and long-term shear conditions (contact stress: ∼12 MPa, friction 5000 cycles). This strategy provides a reference for surface modification of medical interventional devices.

Keywords:  articular cartilage; hydrogel; hydrogel modification; interfacial bonding; lubrication and friction

DOI:  https://doi.org/10.1002/smll.202514771
Small. 2026 Feb 26. e06184

Engineered Protein-Cellulose Composite Hydrogels with Superior Mechanical Performance for Bioadhesion.

Juya Jeon, Zhenqin Wang, Huiyong Li, Manjula Senanayake, Sai Venkatesh Pingali, Hanxun Jin, Kok Zhi Lee, Shri Venkatesh Subramani, Larisa Belaygorod, Batool Arif, Ying Yu, Guy M Genin, Marcus Foston, Mohamed A Zayed, Fuzhong Zhang.

  Strong underwater-setting adhesives hold transformative potential for tissue repair, yet achieving a combination of high adhesive strength, toughness, energy dissipation, and biocompatibility remains a critical challenge. To address this, we engineered a protein-cellulose composite hydrogel composed of microbially-produced hybrid proteins that incorporate silk, amyloid, and mussel foot protein (SAM) domains with polydopamine (PDA)-functionalized cellulose nanocrystals (CNCPDA). The PDA coating enables robust interfacial interactions between the CNC nanofillers and the SAM protein matrix, dramatically enhancing mechanical performance. Hydrogels containing 10% CNCPDA achieved a tensile strength of 4.9 ± 0.9 MPa, strain of 770% ± 33%, toughness of 17 MJ/m3, and damping energy of 202 ± 35 kJ/m3-representing 4.7-, 2-, 3.6-, and ninefold increases, respectively, compared to the unreinforced SAM hydrogel. Pre-stretching further aligned CNCPDA nanofillers within the matrix, enabling tunable enhancement in tensile modulus and ultimate strength. Critically, the composite hydrogels demonstrated strong adhesion to biological tissues, with adhesive strengths of 0.88 ± 0.25 MPa on porcine skin and 1.1 ± 0.3 MPa on bovine bone, far exceeding clinical thresholds for mechanical-demanding tissue adhesives, while maintaining biocompatibility. This synergistic integration of programmable protein design and functionalized nanomaterials provides a versatile platform for next-generation bioadhesives, addressing key unmet needs in bone repair and regenerative medicine.

Keywords:  amyloid beta‐peptides; bio‐adhesive; cellulose nanocrystal; composite hydrogel; mussel foot protein; polydopamine; protein materials; synthetic biology; underwater adhesive

DOI:  https://doi.org/10.1002/smll.202506184
ACS Appl Bio Mater. 2026 Feb 22.

3D Bioprinting of Continuous Nanofibrous Yarn-Reinforced Cell-Laden Constructs.

John Joseph, Niji Nandakumar, Arunkrishnan P R, Helna Mary Baby, Riju Roy Chowdhury, Shantikumar V Nair, Binulal N Sathy, Deepthy Menon.

  Despite notable progress, 3D-bioprinted constructs exhibit limited mechanical robustness and lack the essential ECM-mimicking features crucial for promoting bioactivity, cell growth, and tissue formation. To address these shortcomings, we devised an innovative technique that reinforces bioprinted constructs with polymeric nanofibrous yarns composed of thousands of nanofibers. Utilizing an in situ printing process, a continuous strand of nanofibrous yarn was embedded within the core of the extruded bioink to fabricate a 3D-printed construct. We optimized the key design parameters of the nanofibrous yarn, bioink, and the printing process, which are necessary for direct bioprinting of a nanofibrous yarn-reinforced 3D construct, which has never been demonstrated before. The hydrophilicity of the nanofibrous yarns promoted interfacial interaction with the bioink, while the shear stress developed at the nozzle during extrusion allowed the nanofibrous yarns to be spooled out as a single continuous strand integrated with the bioink. The micron-sized channels within the bundled nanofibrous yarn facilitated cell wicking into the nanifibrous yarn. This approach has enhanced the ability to manufacture cell-laden structures, whereby live cells are freely incorporated into a highly organized nanofibrous architecture. The resulting construct offers the high bioactivity needed for cell regeneration and the superior structural integrity required for diverse biomedical and regenerative medicine applications.

Keywords:  bioprinting; cellular constructs; in situ extrusion; nanofibrous yarns; yarn-reinforced bioink

DOI:  https://doi.org/10.1021/acsabm.5c01703
bioRxiv. 2026 Feb 15. pii: 2026.02.14.705909. [Epub ahead of print]

Programmable and Switchable RNA Scaffolds for Synthetic Condensate Engineering in Mammalian Cells.

Zhaolin Xue, Oyeshik Mukherjee, Lan Mi, Yizhan Guo, Ru Zheng, Chang Yuan, Mingxu You.

The ability to engineer synthetic biomolecular condensates in living cells offers new opportunities to control intracellular organization, yet robust and programmable RNA-based systems have remained limited. Here, we introduce genetically encoded, modular platforms that generate RNA-driven condensates using nanostar-derived scaffolds. Systematic comparison of repeat-based and de novo designs identified nanostar variants that reliably assemble nuclear condensates in mammalian cells. Unexpectedly, condensate formation in cells is governed primarily by double-stranded RNA stems that recruit endogenous RNA-binding proteins, rather than by the kissing-loop interactions that drive assembly in vitro . This mechanistic shift highlights the divergence between cellular and in vitro environments and accounts for the limited orthogonality among scaffolds. Sequence refinement to reduce nonspecific pairing improved homotypic assembly and enhanced orthogonality. We further demonstrated functional compartmentalization by recruiting protein and RNA clients to modulate their stability and activity, and we incorporated an acyclovir-responsive allosteric switch to achieve reversible, small-molecule control of condensation. Together, this work establishes a versatile RNA-based toolkit for constructing programmable cellular compartments, advancing strategies for controlling RNA-protein organization and enabling new biosensing and therapeutic applications.

DOI: https://doi.org/10.64898/2026.02.14.705909
ACS Appl Bio Mater. 2026 Feb 24.

Hierarchical Logic Control via DNA Polymerase-Driven Molecular Circuits.

Siqi Hou, Xuan Liu, Jiongjiong Teng, Mengting Ji, Cheng Zhang, Jing Yang.

  DNA is considered an ideal medium for constructing molecular circuits due to its high programmability and exceptional information density. Current DNA-based circuits are primarily constructed by using toehold-mediated strand displacement (TMSD) or enzyme-assisted reactions. While TMSD-based systems can perform logical operations, their functionality relies heavily on precise base pairing, resulting in complicated design processes and limited scalability. In contrast, enzyme-driven circuits offer a simplified design and support functional diversification. In this study, we developed a DNA polymerase-driven circuit that establishes a system-level programming framework for managing complex molecular states. By regulating strand binding, we defined three stable operational modes: OFF, ON, and the Blocked state (BLC). Based on this mechanism, programmable logic gates were constructed to achieve controllable computing operations. The system incorporates a modular input domain design, enabling dynamic switching among operational modes in response to different input signals: matched inputs specifically activate the target circuit, whereas mismatched inputs drive nontarget circuits into a blocked state. This programmability supports multilevel logical access control and path backtracking, mimicking computer directory mechanisms. Furthermore, this architecture enables conditional signal isolation and regulation, providing an innovative strategy for the hierarchical organization and state-aware management of complex molecular information systems.

Keywords:  DNA circuit; hierarchical access; hierarchical logic control; information processing; logical computing

DOI:  https://doi.org/10.1021/acsabm.5c02582
Nat Commun. 2026 Feb 21.

Engineering non-exponential proliferation in Escherichia coli using functionalized protein aggregates.

Ronald Van Eyken, Dries Oome, Kevin Broux, Sam Jordens, Abram Aertsen.

Microbes naturally grow exponentially, but this trait might not always be desirable for applications with genetically modified microorganisms. Especially in microorganisms engineered for therapeutic applications, uncurbed exponential proliferation might cause unpredictable liabilities in their behavior that in turn compromise their dosing and biocontainment. In an effort to fundamentally reprogram population growth dynamics, we constructed a bacterial chassis that adheres to linear proliferation for a finite number of generations. More specifically, growth of the chassis is directed by an intracellular protein aggregate that is engineered to reconstitute a split enzyme producing cAMP as a conditionally essential metabolite. Due to the asymmetric segregation and gradual disaggregation of this aggregate, it autonomously keeps growth restricted to the aggregate inheriting cell and to a limited number of divisions. By imposing such a transient and linear growth potential without the need for external intervention, this chassis offers a unique venue for the controlled application of engineered microorganisms.

DOI: https://doi.org/10.1038/s41467-026-69334-y
Adv Mater. 2026 Feb 25. e20519

Building like a Coral-Parallelized, Multiscale Biofabrication.

Asma Rehman, Marta Peña Fernández, Kristina K Beck, Gavin L Foster, Sebastian J Hennige, Uwe Wolfram.

  Visible from space or residing in the depths of the ocean, scleractinian corals engineer vast ecosystems supporting high biodiversity and providing essential ecosystem services. By creating these ecosystems, corals address significant challenges in material science, generating skeletal materials that are stiff, strong, and inherently circular-even in conditions where energy and building resources can be scarce or energetically expensive to synthesize. Understanding coral skeletal materials has progressed due to their exceptional mechanical properties, potential biocompatibility, and, in case of cold-water corals, their ability to be synthesized in darkness, at low temperature, and with limited energy resources. These natural, sustainable processes offer inspiring blueprints for the development of transformative new materials, which may drive radical innovations across biomedical and engineering applications. In this perspective, we synthesize the current state of knowledge on the biomineralization process of corals, including the two prevailing viewpoints-biologically controlled vs. physicochemical controlled biomineralization. We then recast coral growth as a multiscale, parallelized biofabrication process, that can catalyse the development of next-generation materials technologies. These insights outline pathways to sustainable, self-organising, and energy-efficient manufacturing with broad relevance to structural materials, biomaterials, and regenerative engineering. Ultimately, we strive to answer: "How to build like a coral?"

Keywords:  aragonite; biomineralization; calcification; cold‐water corals; scleractinian corals; structural materials; sustainable manufacturing

DOI:  https://doi.org/10.1002/adma.202520519
ACS Nano. 2026 Feb 23.

Mechanically and Functionally Resilient Piezoelectric Fiber Coils and Knots for Reliable Self-Powered Sensing.

Yong Jun Choi, JungHun Park, Jisoo Nam, Gi-Dong Sim, Myung-Gil Kim, Miso Kim.

  Electrospun poly(vinylidene fluoride-co-trifluoroethylene) (P(VDF-TrFE)) piezoelectric nanofibers are attractive for self-powered sensing owing to their flexibility and ability to convert mechanical deformation into electrical signals. However, achieving a fully electrode-integrated piezoelectric fiber coil sensor that combines high stretchability with long-term reliability remains a major challenge. Here, we present a mechanically and functionally resilient piezoelectric coil sensor enabled by a hierarchical design that unites a styrene-ethylene-butylene-styrene (SEBS)-assisted interlocked fiber-particle network with a multicomponent-doped poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)/P(VDF-TrFE) electrode that forms a gradient interfacial layer. The fully integrated coil sensor exhibits stretchability up to 668% and maintains stable electromechanical performance under large strains and repetitive loading. The optimized sensor exhibits linear and stable piezoelectric responses to stretching, bending, and compression stimuli, enabling quantitative multimodal mechanical sensing, which is further validated by supervised machine learning classification. In addition, its adaptive knot configurations, such as reef and grief knots, maintain consistent self-powered output under high loads, demonstrating structural adaptability for various stress-monitoring applications. This work establishes a fiber-based self-powered sensing platform that achieves simultaneous mechanical recoverability and electrical robustness through a hierarchical resilient design, offering a versatile route toward wearable healthcare, soft robotics, and surgical assistance.

Keywords:  PEDOT:PSS; coil; electrospinning; piezoelectric fiber; poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)); self-powered sensor

DOI:  https://doi.org/10.1021/acsnano.5c19628
ACS Macro Lett. 2026 Feb 25.

Bottlebrush Polymers for Multiphoton 3D Laser Printing.

Moritz P Hopp, Samantha O Catt, Sachin Gupta, Chenyou Zhang, Markus Müllner, Eva Blasco.

Multiphoton 3D laser printing (MPLP) serves as a powerful tool for shaping materials into complex microstructures with high precision, resolution, and fidelity. Hereby, MPLP predominantly relies on linear prepolymers, while the potential of more complex polymer architecture remains largely unexplored. Bottlebrush polymers (BBPs), characterized by densely grafted side chains emanating from a singular backbone, offer unique properties that could expand the capabilities of MPLP. Herein, a new class of inks for MPLP, based on BBPs, is investigated and systematically evaluated in terms of their printability and mechanical performance. BBPs with different backbone lengths were synthesized and 3D printed to examine the influence of the polymer architecture. Through in-depth characterization of the resultant printed structures using scanning electron microscopy, Fourier-transform infrared spectroscopy, and nanoindentation, the BBPs are shown to have superior printability as well as softer mechanical properties, when compared to linear analogues. By introducing architecturally complex polymers to MPLP, this work expands the material design space for advanced 3D microfabrication and opens new opportunities for application-driven structures requiring tailored properties and functionality.

DOI: https://doi.org/10.1021/acsmacrolett.6c00027
Nat Biotechnol. 2026 Feb 24.

Highly mutagenic continuous evolution in E. coli using a Φ29-based orthogonal replication system.

Fabian B H Rehm, Kim C Liu, Rongzhen Tian, Jason W Chin.

Organisms that permit hypermutation of target genes without off-target mutagenesis of the host genome enable the accelerated, continuous evolution of genes for new or enhanced functions. We develop and optimize an orthogonal DNA replication system in Escherichia coli that uses components from bacteriophage Φ29. The minimal system requires just two Φ29 genes to maintain the replicon and replicons can be efficiently engineered in vivo. We generate a highly mutagenic Φ29 DNA polymerase that introduces mutations at a frequency approaching 10-4 per base per generation (one mutation in a 1-kb gene every ten generations). Our system is stable for hundreds of generations and enables the continuous, accelerated evolution of new gene functions. We demonstrate the rapid evolution of a tetracycline resistance gene to confer resistance to tigecycline at higher levels than achieved with previously reported systems. We further evolve a 1,000-fold increase in β-lactamase activity for a third-generation cephalosporin in just 3 days.

DOI: https://doi.org/10.1038/s41587-025-02944-x
Proc Natl Acad Sci U S A. 2026 Mar 03. 123(9): e2534387123

From peptides to DNA: All required steps can be catalyzed.

Lei Shi, Mériem Senissar, Kirsten Leistner, Carsten Jers, Ivan Mijakovic.

  Ensuring information flow (heredity) and metabolic processes (catalysis) are two important prerequisites for early evolution. The widely accepted "RNA world" theory proposes that ancient RNAs ensured both heredity and catalysis during the transition from prebiotic to biotic evolution. However, alternative hypothetical molecules and processes have also been proposed, suggesting that catalytic peptides may have existed before polynucleotides, and that their sequences were later reverse translated into genes. Our objective was to experimentally address these alternative theories by asking whether the steps required for the hypothetical conversion of peptide sequences into DNA could be catalyzed by the existing molecular kit. The reactions we tested comprise i) step-wise degradation of peptides by a processive amino peptidase, sequentially releasing amino acids, ii) matching the identity of released amino acids to codons by aptazymes (RNA adapters that recognize amino acids and self-cleave and release specific codon triplets in response), and iii) ligating codon triplets into longer RNAs that can be reverse-transcribed into DNA. In a hypothetical processive system based on these reactions, the resulting DNA sequence would match the sequence of amino acids in the starting peptide. Our results suggest that all these steps can be catalyzed, and therefore the possibility of reverse translation occurring at some point in early evolution should not be disregarded.

Keywords:  amino acid-to-codon matching; catalytic RNA; prebiotic evolution; processive aminopeptidase; reverse translation hypothesis

DOI:  https://doi.org/10.1073/pnas.2534387123
bioRxiv. 2026 Feb 20. pii: 2026.02.19.706875. [Epub ahead of print]

Rational design of synthetic proteins using a genome-scale CRISPR screen.

Wells H Burrell, Simon J Mueller, Zharko Daniloski, P Duffy Doyle, Anne B Rovsing, Christopher James, Max Drabkin, Chien-Yu Chou, Hei Yu Annika So, Lyla Katgara, Akash Sookdeo, Lu Lu, Georges-Ibrahim Cisse, Rachel E Yan, Neville E Sanjana.

Protein structure prediction using deep learning has revolutionized protein design. Yet, our understanding of protein function remains a key limitation for designing novel proteins that perform complex biological tasks. Here, we adopt a massively-parallel, function-first approach to rationally design synthetic proteins. Using genome-scale CRISPR activation, we overexpress ∼19,000 human proteins and measure their impact on precise gene editing. We identify over 800 native proteins that promote homology-directed repair. Using top candidates, we then design synthetic genome editors - Targeted Repair fUsion Editors (TruEditors) - by fusing full-length proteins or smaller core domains to the Cas9 nuclease. We develop 12 unique TruEditors that improve precise gene editing in diverse cell types and at genomic loci where existing methods for precise gene editing fail. Using affinity proteomics, we show that these synthetic proteins work by coordinating with endogenous DNA repair complexes. The delivery of TruEditors via mRNA more than doubles the rate of chimeric antigen receptor (CAR) insertion into the TRAC locus of primary human T cells, enhancing CAR T cell-directed tumor cell killing, and improves precise editing in human pluripotent stem cells more than three-fold. Overall, our study demonstrates that genome-wide protein overexpression screens can guide the rational design of synthetic proteins for specific biological tasks.

DOI: https://doi.org/10.64898/2026.02.19.706875
Eng Life Sci. 2026 Feb;26(2): e70066

The Impact of Fungal Developmental Structures on Mechanical Properties of Mycelial Materials.

Kelsey Gray, Harley Edwards, Alexander G Doan, Walker Huso, JungHun Lee, Wanwei Pan, Nelanne Bolima, Isha Gautam, Tuo Wang, Ranjan Srivastava, Marc Zupan, Mark R Marten, Steven D Harris.

  This study explores how suppressing asexual development in Aspergillus nidulans enhances the mechanical properties of mycelial materials. Using four aconidial mutants (∆brlA, ∆flbA, ∆fluG, and fadAG42R ) lacking asexual development and a control strain (A28) that undergoes typical asexual development, we found that the absence of asexual development significantly improves mechanical strength. All mutants exhibited higher ultimate tensile strength (UTS) than the control, with ∆fluG and ∆brlA (fluffy nonsporulating, FNS phenotype) showing the highest UTS. Additionally, fadAG42R and ∆flbA (fluffy autolytic dominant, FAD phenotype) demonstrated significantly higher strain at failure (SF), linked to increased autolysis and lower dry cell mass compared to the control and FNS mutants. Solid-state NMR analysis suggests that autolysis in FAD mutants may disrupt galactofuranose-related processes, altering cell wall composition and contributing to higher elasticity. These findings suggest suppression of asexual development increases mycelial material strength, while autolysis mechanisms influence elasticity. This research highlights the potential for genetic manipulation in fungi to engineer advanced mycelial-based materials with tailored mechanical properties.

Keywords:  Aspergillus nidulans; asexual development suppression; cell wall composition; engineered living materials (ELMs); mechanical properties

DOI:  https://doi.org/10.1002/elsc.70066
bioRxiv. 2026 Feb 22. pii: 2026.02.20.707066. [Epub ahead of print]

Tensile expansion microscopy applies mechanical force to super-resolve fixed and image live cellular samples.

Vignesh Venkataramani, Danielle R Latham, Ramita Arampongpun, Marouen Zammali, Tejasvin Shrikanth, Anshuman Mohapatra, Jason A Guerrero, Roberto C Andresen Eguiluz, Divita Mathur, Laura M Sanchez, Lydia Kisley.

Understanding biophysical phenomena requires techniques that access biologically relevant spatial and temporal scales. Expansion Microscopy (ExM) is a sample preparation approach which achieves super-resolution spatial scales by leveraging osmotic forces in a swellable hydrogel to physically separate structures to distances larger than the diffraction limit of light. Yet, in traditional osmotic ExM only pre- and post- expanded samples can be imaged. Further, fragmentation, hydrogel deformation, and signal loss are common while requiring samples to be chemically fixed. Therefore, there is little control of the expansion, reproducibility can be challenging, and dynamics of biological samples at applicable temporal scales cannot be observed. Here, we develop Tensile Expansion Microscopy (TExM) to mechanically expand fixed and, notably, living cellular samples. Highly-stretchable and tough double network alginate- Ca 2+ /polyacrylamide hydrogels are expanded by tensile forces applied using an electromechanical iris expansion device during continuous imaging on a fluorescence microscope. We incorporate two-photon polymerized microscale fluorescent fiducial markers to track samples and distortion during expansion. The hydrogels controllably and repeatedly expand up to 3.3× with distortions less than 12 µm across 1.3 mm 2 . TExM is first applied to fixed NIH 3T3 fibroblast cells with immunohistochemistry-stained microtubules, achieving super-resolutions of 100 nm. Then, TExM is demonstrated with living HeLa cells with internal fluorescent reporters showing increased cell size and cell-to-cell separation under 3.2× linear expansion. Overall, TExM allows for continuous, stepwise, and precise temporal modulation of lateral substrate strain, enabling real time monitoring of dynamics of both fixed and viable live cell processes at higher spatial resolutions. TExM can further investigate broad biophysical questions due to its compatibility with other analytical imaging methods that are sensitive to water or fixatives used in traditional osmotic ExM.

DOI: https://doi.org/10.64898/2026.02.20.707066
J Colloid Interface Sci. 2026 Feb 16. pii: S0021-9797(26)00301-2. [Epub ahead of print]712 140124

Proteoliposomes containing ATPase as microreactors to mimic microbial metabolism for bioenergy synthesis.

Xuanze Meng, Yang Xu, Yi Jia, Rong Shu, Zibo Li, Junbai Li.

  Learning and imitating the inherent metabolic pathways of organisms in nature has emerged as a crucial approach to achieve artificial biomimetic synthesis of Adenosine triphosphate (ATP). We have constructed a biomimetic microreactor inspired by the ethanol metabolism pathway in microorganisms. The alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) loaded in the microreactor can catalyze the cascade reaction of ethanol to acetic acid. This proton-producing reaction is spatially coupled with the ATP synthase embedded in proteoliposomes, establishing a transmembrane proton gradient that drives ATP synthase to synthesize ATP. The generated ATP concentration can reach up to 6.3 μM within 30 min, which is rather high. The microreactors effectively reconstruct the core step of acetic fermentation process to convert chemical energy into bioenergy. This work demonstrates a novel and efficient route to transform low-value, readily available basic chemical products into universal biological energy carrier ATP, bypassing the need for intricate metabolic networks. Such a design provides a foundational model for understanding and engineering cellular metabolism.

Keywords:  ATP synthase; Cascade reaction; Energy conversion; Nanoarchitecture; Supramolecular assembly

DOI:  https://doi.org/10.1016/j.jcis.2026.140124
ACS Nano. 2026 Feb 25.

DNA Framework-Encoded Digital Recorder for Bacterial Discrimination.

Chenghao Xi, Junheng Zhang, Lu Song, Yueyue Zhang, Shaopeng Wang, Mingqiang Li, Fei Wang, Chunhai Fan, Hua Wang, Xiaolei Zuo, Min Li.

  The ability to discriminate multiple biomolecular signals simultaneously is critical for accurate diagnosis of coinfections and evaluation of the medical environment. Yet, achieving multichannel enumeration within a single recording unit remains a significant challenge. Here, we develop a DNA framework-based positional encoding system, termed the DNA Framework Digital Recorder (DFDR), which enables site-specific discrimination of multiple nucleic acid sequences using a uniform signal reporter. The DFDR is composed of a triangular DNA framework where each edge is site-specifically functionalized with orthogonal probes targeting distinct DNA sequences. We demonstrate that a single DFDR unit can resolve 18 nucleic acid targets simultaneously, 6-fold of the multiplexing capacity over conventional DNA self-assembly-based identification systems. Through temporal control of DNA strand inputs, the DFDR supports sequential and rewritable recording of multiplexed signals. We further validate the system by discriminating 16S rRNA mixtures from clinically relevant respiratory pathogens (Haemophilus, Klebsiella, Staphylococcus, and Lactobacillus). Finally, we demonstrate bacterial identification in real-world samples collected from the hospital environment and natural river water. This work establishes a versatile paradigm for high-resolution tracking of multiplexed molecular information with broad implications for synthetic biology, diagnostics, and information storage.

Keywords:  DNA framework; bacteria detection; biosensor; nucleic acid analysis; position encoding

DOI:  https://doi.org/10.1021/acsnano.6c01091
Nano Lett. 2026 Feb 25.

Compliant and Tough Triboelectric-Piezoresistive Porous Hydrogels Enabled by Interfacial Assembly of Nanocellulose Microgels.

Yang Yang, Xiaofang Liao, Kang Yu, Mingchao Chi, Chenchen Cai, Song Zhang, Qiguan Luo, Zhiwei Wang, Shuangfei Wang, Shuangxi Nie, Peng Lu.

  Flexible hydrogel materials capable of multimodal sensing are ideal candidates for multidimensional interactive tactile systems. However, conventional approaches based on physically integrated discrete sensors often lead to structural complexity and mechanical compromise. Here, this study proposes an interfacial assembly strategy based on monomer-swollen microgels to prepare a monolithic triboelectric-piezoresistive porous hydrogel with enhanced mechanical flexibility. The tailored porous architecture reduces the hydrogel's modulus from 216.2 kPa to 20.4 kPa, while maintaining excellent mechanical toughness of 329.4 kJ m-3 and high porosity (73.6%). It also enhances triboelectric output (power density of 0.32 W m-2) and micropressure sensitivity (increased from 25.9 kPa-1 to 193.8 kPa-1 in the 0-200 Pa range). The integrated wearable sensor demonstrates accurate tactile pattern recognition and material discrimination, enabling decoupled and independently quantified dynamic and static tactile stimuli. This study provides a viable strategy for designing simplified, high-performance flexible hydrogel substrates suitable for complex sensing applications.

Keywords:  Interface assembly; Multimodal sensing; Triboelectric nanogenerators; Triboelectric-piezoresistive composite hydrogels; Wearable sensors

DOI:  https://doi.org/10.1021/acs.nanolett.5c06498
Small. 2026 Feb 25. e14534

A Versatile Zwitterionic Gelation Strategy Triggered by Phenol-Modified Biomacromolecules: Facile Synthesis of Bioactive and Customizable Hydrogels.

Zhiliang Han, Wufei Ge, Fangyi Guan, Zhenguang Li, Xiangyang Qu, Mengyao Guan, Chen Zhu, Xianzuo Zhang, Shiyan Chen, Huaping Wang.

  The functionalization and biological activity of hydrogel interfaces are significant for implantation and therapeutic applications. By introducing various monomers or additives during conventional gelation processes, facile functional modification and biological activity regulation of hydrogels can be achieved. However, these methods face challenges of potential toxicity and the preparation procedure. Here, we report a phenol-triggered universal gelation strategy involving solely phenol-modified biomacromolecules and zwitterionic monomers, which achieves superior biocompatibility. Significantly, this strategy exhibits universality for common biomass (e.g., polysaccharides and polypeptides), as well as for phenols, enabling substantial scope for functional diversification and application. The hydrogels are prepared by branching on the biomacromolecules, which imparts modular physicochemical and biomedical properties. Furthermore, simply by modulating substrate composition and performing rapid surface treatment, the hydrogel interfaces can regulate biological activities including cell adhesion and antifouling properties. This work presents a universal gelation strategy that offers an effective and promising approach for the design of biointerfaces.

Keywords:  biological activity; biomacromolecules; hydrogel interfaces; phenol; zwitterions

DOI:  https://doi.org/10.1002/smll.202514534