bims-enlima 2026-06-07 papers

bims-enlima

Biomed News

on Engineered living materials

Issue of 2026–06–07
34 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool

3D Printing of Enzymatically Softening Hydrogel Biomaterials.
Mechanically Programmable DNA Hydrogel Microparticles for 3D Cellular Systems.
Controlling 3D Contractility via Engineered Fibrous Hydrogel Composites.
Light-based 3D printing of mechanoluminescent living gels loaded with dinoflagellates.
Hierarchical Programming of Peptide Hydrogels via Electrostatic Coassembly and Dityrosine Cross-Linking.
Mechanical Training-Induced Restructuring Enables Self-Extendability and Mechanical Consistency in Organohydrogels.
Biofunctionalized polymer semiconductors toward soft and stretchable transistor-based biosensors.
Multimodal control of Cas13d activity through domain insertion at an allosteric hotspot.
Molecular Engineering Mediated Interfacial Assembly as an Artificial Extracellular Matrix Remolds Bacteria With Enhanced Abiotic Resilience.
Self-Assembling Cationic Lipopeptides for the Construction of Functional Vesicular Gene-Delivery Systems.
Image-based phenotypic sorting of synthetic cells.
Mechanophore cross-linking enhances ballistic energy dissipation of polymers.
Engineered Bacteria as Living Materials for Oral Delivery of Peptide Drugs.
An engineered streptavidin condensate platform for chemically inducible control of endogenous proteins in mammalian cells.
Programmable Nucleic Acid Sensing in Human Cells Using Circularizable ssDNA.
Topology Optimization of 3D-Printed Mycelium Hydrogels.
Direct White-Light Reconfiguration of Dynamic Covalent Polymer Networks via Photoinsertable Spirothiopyran.
Why a synthetic human genome is still worth building.
ATP is dispensable for E. coli DNA replication and eukaryotic helicase activity.
Silk-Based Protein Corona Enhances mRNA-LNP Vaccine Efficacy and Prevents Tumor Relapse.
High-throughput engineering of ligand-activated splicing ribozyme through domain insertion.
Engineering Apical Integrin-Binding Cellular Patches to Direct Cell Reprogramming via Mechanical Remodeling.
Defining the rules of biocompatible chemistry.
Ratiometric transcriptional activation by protein degradation.
Tracking microstructure and mechanical response.
In-Situ Metabolic Profiling of Single Living Cells by Liquid Secondary Ion Mass Spectrometry.
Decoupling Stiffness and Toughness in Solid Polymer Electrolytes via Reversible Crystallization.
Setting Boundaries: Surface Engineering of Viral-Inspired Materials.
Nascent protein retention at polysomes reduces kinetic barriers to self-assembly.
Label-free interferometry platform for drug response profiling of bioprinted tumor organoids at single-organoid resolution.
Engineered Cellulose Nanofiber/SiC Nanowire Films via Combustion Synthesis and Alignment for High-Performance Flexible Thermal Management.
Engineering a GelMA Hydrogel-Based Biomimetic Endometrium-on-a-Chip for Studying Embryo Implantation.
Bioinspired spatiotemporal control of microhelix formation and actuation.
Achieving cell-type-specific bioorthogonal chemistry using enzyme-activated caged tetrazines.

Regen Eng Transl Med. 2025 Dec;11(4): 1099-1108

3D Printing of Enzymatically Softening Hydrogel Biomaterials.

Olivia P Dotson, Sherina Malkani, Inkyung Kang, Cole A DeForest, Kelly R Stevens.

   Purpose: 3D printing has accelerated tissue engineering by enabling rapid fabrication of bioprinted tissues from a variety of soft biomaterials. Yet, an ongoing challenge is that for many bioprinting technologies, the materials (bioinks) need to be printed "stiff" (i.e., G' > ~ 15 kPa) so that the fabricated tissue constructs retain high resolution and shape fidelity. Conversely, softer materials tend to generally be more supportive of cellular phenotype and function. To bridge this gap, we sought to develop a hydrogel system that would expand bioprinting access to softer materials, while retaining the resolution of fabricated spatial features.
Methods: We developed a photopolymerizable copolymer hydrogel system consisting of nondegradable synthetic and proteolytically degradable natural polymers. Varying the overall polymer content, as well as the ratio between the poly(ethylene glycol) and gelatin species, we generated a library of lithographically printable hydrogel formulations with differing initial stiffnesses that could be further variably softened following enzymatic treatment using collagenase.
Results: Varying the copolymer composition and overall concentration resulted in the creation of gels whose initial stiffness ranged from 82 to 2 kPa and could be subsequently softened up to 20-fold upon enzymatic treatment. When 3D-printed via digital light processing (DLP), softened gels maintained higher structural integrity than those with matched initial stiffness. Softened gels supported greater endothelial cell perfusion-based seeding compared to those untreated while maintaining high cell viability.
Conclusion: Our material system presents a simple solution to the ongoing challenge of 3D-printing soft materials with high resolution.
Future Work: In future studies, we will develop post-print softening materials with bio-invisible stimuli to expand applications to in vivo softening of biomaterial tissue mimics.
Lay Summary: 3D-printing has become popular in tissue engineering applications, but printing complex, organ-like structures with soft materials remains challenging. We created a material that can hold patterned shapes and small printed structures using a post-print softening technique with a degrading enzyme. We found that different formulations of this hydrogel material offer varying stiffness levels (G' = 2 kPa-82 kPa) and can soften up to 20-fold with enzymatic treatment. Notably, this material retains the structure of 3D-printed open channels even after significant softening, and cells respond well when seeded in these channels. This demonstrates the promise of post-print softening to create soft 3D-printed materials.

Keywords:  3D-printing; Biomaterials; Hydrogel; Tissue engineering

DOI:  https://doi.org/10.1007/s40883-025-00445-6
Adv Mater. 2026 May 31. e14218

Mechanically Programmable DNA Hydrogel Microparticles for 3D Cellular Systems.

Tobias Walther, Eleni Dalaka, Gotthold Fläschner, Manuel Gómez-González, Ilia Platzman, Sadaf Pashapour, Michelle Emmert, Pere Roca-Cusachs, Xavier Trepat, Kerstin Göpfrich.

  Hydrogel microparticles (HMPs) are powerful tools to study and manipulate cellular behavior in 3D cell culture systems and animal models. Here, fully DNA-based HMPs are presented, whose material properties can be precisely tuned by sequence-programmable design of self-assembling DNA nanostructures. These DNA-HMPs offer control over size, stiffness, viscoelasticity and ligand presentation. They are formed by microfluidic encapsulation of two types of orthogonal DNA nanostars and a sequence-complementary DNA linker in water-in-oil droplets. By varying the valency of the DNA nanostar designs, tunable mechanical properties are achieved - spanning three orders of magnitude in Young's modulus from 30Pa$30 \,\mathrm{Pa}$ to 6.5kPa$6.5 \,\mathrm{k}\mathrm{Pa}$ with distinct viscoelastic behavior. Click-chemistry based functionalization with the small fibronectin-derived peptide cyclic-RGD (c[RGD]) enables integration into fibroblast spheroids. DNA-HMPs are stably retained within the spheroids for several days and undergo remodeling, indicating active interactions between the cells and the DNA-HMPs. Combining programmable material properties and inherent biocompatibility of DNA with straightforward functionalization and stimuli-responsiveness, these DNA-HMPs represent a versatile tool to probe and manipulate tissue behaviors in 3D cell cultures.

Keywords:  3D cell culture; DNA hydrogel; DNA nanotechnology; biomaterials; hydrogel microparticles; mechanobiology; microfluidics

DOI:  https://doi.org/10.1002/adma.202514218
Adv Funct Mater. 2026 May 04. pii: e24101. [Epub ahead of print]36(36):

Controlling 3D Contractility via Engineered Fibrous Hydrogel Composites.

Karen L Xu, Yuqi Zhang, Alysse DeFoe, Georgios Kotsaris, Brendan Stoeckl, Matthew D Davidson, Jason A Burdick, Robert L Mauck.

  Complex and dynamic mechanobiological crosstalk occurs between cells and their extracellular matrix (ECM) to support contraction, a process required for tissue morphogenesis and wound healing. In vitro models can be used to study this crosstalk by mimicking the ECM (collagen fibers within a ground substance) using controlled environments and defined mechanics. While useful, most in vitro models utilize poorly-defined natural hydrogels that lack independent control over hydrogel properties and contraction tunability. Here, a fully-defined hydrogel composite is introduced consisting of fragmented synthetic fibers (a collagen fiber mimic) that, when embedded within a synthetic hydrogel (a ground substance mimic), supports cell-mediated traction-based contraction in a manner similar to traditional collagen gels. Tuning this composite material by modulating fragmented fiber density and length and embedding hydrogel density and crosslinking enables control over contraction. Cells cultured within contraction-permissive constructs support microtissue cell alignment and local densification of fiber fragments, while culture in contraction-resistant composites (greater embedding hydrogel crosslinking) do not. This innovative composite material expands our ability to interrogate the complex cell-ECM interplay during tissue morphogenesis.

Keywords:  contraction; electrospun fibers; hyaluronic acid; hydrogels; microtissues

DOI:  https://doi.org/10.1002/adfm.202524101
Sci Adv. 2026 Jun 05. 12(23): eadz0017

Light-based 3D printing of mechanoluminescent living gels loaded with dinoflagellates.

Rani Boons, Mathias Steinacher, Henning Galinski, Vincent Niggel, Tanja Zimmermann, Gustav Nyström, Gilberto Siqueira, André R Studart.

Dinoflagellates, a group of marine unicellular algae, are known for the fascinating glowing effects in coastal waters. While this natural mechanoluminescent phenomenon has been explored in pressure sensors and optical transducers, technologies to shape dinoflagellate-containing materials into more complex, engineering-relevant geometries remain limited. Here, we report a three-dimensional printing strategy to manufacture complex-shaped mechanoluminescent objects using dinoflagellates embedded in biocompatible hydrogels. The growth and mechanoluminescence of the entrapped dinoflagellates were investigated by optical microscopy, emission spectroscopy, and mechanical testing of cell-laden gels. Dinoflagellate-laden gels showed strong bioluminescence when compressed at sufficiently high strain and strain rates. By incorporating the dinoflagellates into a photo-curable hydrogel, we shaped such living material into complex geometries using a widely available light-based printing technique. The ability to print dinoflagellate-laden gels into intricate shapes broadens the design space available for the creation of mechanoluminescent living objects for applications in soft robotics, self-powered sensing, and optical transduction.

DOI: https://doi.org/10.1126/sciadv.adz0017
ACS Appl Mater Interfaces. 2026 Jun 02.

Hierarchical Programming of Peptide Hydrogels via Electrostatic Coassembly and Dityrosine Cross-Linking.

Yuhan Qian, Xianan Li, Guoyao Shen, Feili Zhang, Huaimin Wang, Zhaoqianqi Feng.

  The extracellular matrix in living tissues undergoes dynamic mechanical changes that govern fundamental processes in development and disease, yet most synthetic hydrogels are mechanically static and cannot reproduce this programmability. Here, we report a covalent-supramolecular hybrid peptide hydrogel platform that enables two-stage, hierarchical stiffening. A family of short peptides undergoes electrostatic coassembly to form a supramolecular network, producing an order-of-magnitude increase in initial stiffness. Subsequent light-induced dityrosine cross-linking introduces a second, covalent stiffening phase. Remarkably, simple repositioning of tyrosine residues directs the final material architecture: one design yields stiffening fibrous hydrogels, whereas another generates cell-internalized nanospheres. This work demonstrates precise control over mechanical and structural outcomes, providing a programmable bioinspired building block for the development of dynamic biomaterials.

Keywords:  dityrosine cross-linking; electrostatic coassembly; peptide; programmable assembly; self-assembly

DOI:  https://doi.org/10.1021/acsami.6c02238
Small. 2026 May 30. e73981

Mechanical Training-Induced Restructuring Enables Self-Extendability and Mechanical Consistency in Organohydrogels.

Longya Xiao, Jinxin Lai, Shasha He, Quan Hu, Yiwan Huang, Hongjie Jiang.

  Echinoderms, such as sea cucumber, dynamically change their body size to environmental stimuli. By contrast, typical synthetic materials cannot reinvent their structures once formed. We propose a strategy for developing "self-extendability" polymeric materials that can be structurally tuned by repetitive mechanical stress stimulation. Polyion complex glycerol (PICG) hydrogels undergo self-extendability and mechanical consistency, and the materials substantially grow in deformation under repetitive loading through a diffusion of disentangled dense structure to sparse structure. This strategy is generalizable to other polymers and topologies. Additionally, the gel is able to adhere to 3D surface. These advancements make our gels ideal for e-skin substrate materials; they simultaneously offer extended performance and curved surface attachment. This work may open an avenue for the development of self-extendability materials for intelligent devices.

Keywords:  mechanical consistency; organohydrogels; self‐extendability; training‐induced

DOI:  https://doi.org/10.1002/smll.73981
Sci Adv. 2026 Jun 05. 12(23): eaec2641

Biofunctionalized polymer semiconductors toward soft and stretchable transistor-based biosensors.

Chuanzhen Zhao, Qianhe Liu, Jia-Yuan Chang, Aditri Patil, Lukas Michalek, Yilei Wu, Yujia Yuan, Rachael K Mow, Yuran Shi, Yating Yao, Kuang-Jung Hsu, Yu Zheng, Zhenan Bao.

Organic materials with tunable chemical and mechanical properties are ideal for interfacing with skin and tissue in biomedical applications. While polymer semiconductors (PSCs) have advanced toward skin-like mechanical performance, the limited capacity for biofunctionalization has restricted their biosensing applications. In this study, we introduce a direct biofunctionalization strategy for PSCs based on thiol-ene chemistry. We selectively grafted thiolated biomolecules (e.g., aptamers) onto elastomeric domains within an interconnected semiconductor/elastomer network. This approach enables high-resolution patterning down to 10 micrometers while preserving the electronic performance of PSCs. Leveraging this platform, we designed and fabricated skin-like electrolyte-gated organic field-effect transistors with biofunctionalized channels. These soft and stretchable devices exhibit stable operation in physiological buffers for more than 50 days and maintain performance under up to 50% strain. When functionalized with cortisol-binding aptamers, the sensors achieved sensitive detection across physiologically relevant concentrations, down to the picomolar range. This work establishes a foundation for integrating stretchable and biofunctional PSCs into skin-like wearable devices.

DOI: https://doi.org/10.1126/sciadv.aec2641
Nat Commun. 2026 Jun 03.

Multimodal control of Cas13d activity through domain insertion at an allosteric hotspot.

Liyuan Zhu, Long T Nguyen, Alexandra G Bell, Tom Krebel, Kara M Gillmann, Qinhao Cao, Harrison Oatman, Jack Hariri, Andreas Möglich, Cameron Myhrvold, Jared E Toettcher.

CRISPR-Cas13d RNA nucleases are powerful tools for programmable RNA targeting. A light-controlled RNA nuclease could be transformative by enabling researchers to selectively knock down transcripts at desired positions in a cell or tissue or at timepoints of interest. Here, we develop a set of RfxCas13d tools that can be multimodally controlled by either light or small molecule addition. By screening an RfxCas13d library containing insertions of the AsLOV2 photoswitchable domain, we identify an OptoCas13d-off variant that induced target RNA cleavage in the dark and switched to an inactive state under blue light. We show that the same allosteric hotspot can be exploited to generate an OptoCas13d-on with an inverted light response and a ChemoCas13d that is activated by rapamycin analogs, enabling knockdown of endogenous mRNA and protein targets. Overall, our study shows that engineered allostery can produce stimulus-controlled Cas13d variants to modulate RNA with high spatial and temporal precision.

DOI: https://doi.org/10.1038/s41467-026-73645-5
Adv Sci (Weinh). 2026 Jun 03. e75937

Molecular Engineering Mediated Interfacial Assembly as an Artificial Extracellular Matrix Remolds Bacteria With Enhanced Abiotic Resilience.

Yuanyuan Wang, Zili Jia, Yang Li, Qitao Wang, Shuai Hou, Lei Liu.

  Microbial inoculants are central to sustainable agriculture; however, the vulnerability of bacterial cells to desiccation represents a fundamental barrier to their effective use in open-environment applications. While nature employs extracellular polymeric substances for protection, synthetic replication of this multifunctional, nanoscale interface remains a challenge. Here, we report a biomimetic strategy to assemble an artificial extracellular matrix (AEM) directly on the surface of Pseudomonas fluorescens, conferring exceptional abiotic resilience. Inspired by amyloid-protein architecture in natural biofilms, we engineered an interfacial coating via the conformational transition of lysozyme into a β-sheet-rich, adhesive scaffold, which electrostatically co-assembles with alginate polysaccharides at the cell envelope. This conformal nanocoating provides dual-mode protection: it acts as a viscoelastic hydration buffer that prevents membrane rupture, and it elicits a transcriptional response that upregulates genes associated with respiration, osmoprotection, and proteostasis. Optimized at a 1:1 protein-to-polysaccharide ratio, the AEM enhances bacterial survival after desiccation by 30.9-fold. Furthermore, it enables robust seed adhesion and storage stability, translating into effective biocontrol against Fusarium pathogens in a model agricultural system. This work establishes a versatile strategy for programming cellular interfaces, bridging materials design and microbial functionality to engineer resilient living systems for real-world deployment.

Keywords:  artificial extracellular matrix; biomimetic nanocoating; desiccation tolerance; interfacial assembly; microbial biocontrol

DOI:  https://doi.org/10.1002/advs.75937
Small. 2026 Jun 05. e74067

Self-Assembling Cationic Lipopeptides for the Construction of Functional Vesicular Gene-Delivery Systems.

Federica A Souto-Trinei, Alba Ramil-Bouzas, Paco Fernández-Trillo, Ana Rey-Rico, Roberto J Brea.

  Delivering nucleic acids across cellular membranes remains a central challenge. Although synthetic gene carriers that mimic living cells are gaining interest, creating robust and biocompatible compartments continues to be technically demanding and limited in scope. Here, we present a new class of cationic lipopeptides that self-assemble into stable, functional membrane structures, offering a versatile platform for gene-delivery applications. These lipopeptides combine the biological activity and programmability of peptides with the self-organizing behavior of lipids, yielding functional vesicular structures that emulate cellular compartments and act as powerful non-viral vectors. We demonstrate that these assemblies efficiently sequester and deliver nucleic acids, achieving high transfection efficiency with minimal cytotoxicity in HEK 293T cells, and importantly, extending this performance to more challenging cellular models such as mesenchymal stem cells (MSCs). Our findings highlight the potential of self-assembling cationic lipopeptides as modular building blocks for generating robust, biocompatible, and programmable synthetic cells capable of delivering diverse nucleic acids.

Keywords:  gene delivery; lipopeptide; self‐assembly; synthetic cell; vesicle

DOI:  https://doi.org/10.1002/smll.74067
Sci Adv. 2026 Jun 05. 12(23): eaed0860

Image-based phenotypic sorting of synthetic cells.

Marijn van den Brink, Marlena Stam, Nico J Claassens, Christophe Danelon.

Understanding the relationships between genotype and phenotype is key to many areas of biological research and to the development of synthetic cells. We describe an image-based screening and sorting workflow that explores the phenotypes of gene-expressing vesicles within nonclonal populations and selects the desired variants. Using automated confocal microscopy and real-time, neural network-assisted image analysis, we demonstrate that liposomes can be selected for fluorescence intensity, protein localization, membrane morphology, and dynamic behaviors, and their phenotype can be linked to genetic content. This approach could substantially accelerate the evolution of cellular functions in a minimal synthetic context.

DOI: https://doi.org/10.1126/sciadv.aed0860
Nature. 2026 Jun;654(8117): 85-91

Mechanophore cross-linking enhances ballistic energy dissipation of polymers.

Zhen Sang, Suong T Nguyen, Kwangwook Ko, Senpeng Lin, Heecheol Jang, Simon Gonzalez-Zapata, Sullivan Fitz, Yun Kai, Steven Kooi, Chuting Deng, Monica Olvera de la Cruz, Marisol Koslowski, Heather J Kulik, Stephen L Craig, Keith A Nelson, Jeremiah A Johnson.

Mechanical failure is a marked limitation for plastics used in structural, protective and coating applications. In particular, perforation under high-rate deformation is difficult to mitigate through conventional molecular design1,2. Cross-linking is widely used to improve the thermal and chemical stability of polymers, yet under mechanical deformation, it typically renders materials more brittle, limiting impact resistance and functional lifetime3. Overcoming this fundamental trade-off between stability and toughness remains a central challenge. Here we demonstrate that embedding a small fraction of force-sensitive mechanophores as cross-links into common polymers fundamentally reverses this trade-off, producing materials with substantially enhanced ballistic energy dissipation. At strain rates exceeding 107 s-1, we show that mechanophore-cross-linked networks absorb up to about 115% more energy than conventional thermosets and surpass even their uncross-linked thermoplastic counterparts. We attribute this behaviour to a force- and adiabatic-heating-driven local thermoset-to-thermoplastic transition, in which selective mechanophore scission facilitates viscoplastic deformation at the impact site while preserving network integrity in the surrounding regions. We demonstrate the generality of this strategy in both glassy polystyrene and rubbery styrene-butadiene-styrene triblock copolymers. These results establish mechanophore cross-linking as a design principle for converting commodity polymers into impact-resilient materials and open directions at the intersection of polymer mechanochemistry and extreme-strain-rate material behaviour.

DOI: https://doi.org/10.1038/s41586-026-10557-w
ACS Appl Mater Interfaces. 2026 Jun 03.

Engineered Bacteria as Living Materials for Oral Delivery of Peptide Drugs.

Lu Yu, Xiao Han, Jinyuan Liu, Xuehai Yan, Tianyu Li.

  Peptide drugs play a crucial role in treating numerous major diseases due to their high bioactivity, specificity, and biosafety. However, their oral delivery is severely limited by gastric acidity, enzymatic degradation, and poor intestinal absorption, leading to extremely low bioavailability. In recent years, bacterium has emerged as a promising drug delivery platform. Engineered bacteria can colonize the gastrointestinal tract, enabling in situ synthesis and release of therapeutic peptides, thereby offering an effective strategy to overcome the bottlenecks in oral peptide delivery. This review summarizes recent advances in engineered bacteria as "living functional materials" for oral peptide delivery, focusing on the optimization of chassis cells and the mechanisms of peptide release. It systematically outlines their therapeutic applications in metabolic, inflammatory, neurodegenerative diseases, and cancer. Finally, we discuss the emerging potential of intelligent engineered bacterial delivery systems to drive in situ peptide self-assembly, expanding the boundaries of biomaterials and supporting the development of next-generation smart, responsive, and programmable oral peptide delivery systems.

Keywords:  controlled release; engineered bacteria; oral delivery; peptide; self-assembly; synthetic biology

DOI:  https://doi.org/10.1021/acsami.6c06551
bioRxiv. 2026 May 25. pii: 2026.05.22.725644. [Epub ahead of print]

An engineered streptavidin condensate platform for chemically inducible control of endogenous proteins in mammalian cells.

Takuya Kamikawa, Cole J Wilson, Ivy Lan, Yuta Nihongaki.

Inducible control of protein activity with temporal precision is essential for understanding and engineering dynamic cellular behaviors. However, current inducible molecular tools largely rely on overexpression of target proteins, which often disrupts the signaling pathways and cellular functions under investigation. A generalizable method to achieve inducible control of endogenous proteins in mammalian cells remains an unmet need. Here, we present a versatile platform based on engineered streptavidin biomolecular condensates to trap and release endogenously tagged proteins. By tagging endogenous loci with a short streptavidin-binding peptide via CRISPR knock-in, our synthetic streptavidin condensates efficiently partition and functionally inhibit the tagged endogenous proteins. The sequestered cargo protein is rapidly released upon the addition of biotin, restoring protein activity within minutes. We demonstrated the broad applicability of this system by controlling diverse endogenous targets: the anterograde motor KIF5B and retrograde motor DYNC1H1, which regulate intracellular vesicle trafficking, and the Arp2/3 complex subunit ARPC3, which regulates actin dynamics. Furthermore, we developed a dual-inducible system based on rapamycin-dependent condensation of streptavidin, enabling both rapid sequestration and release of endogenous proteins at user-defined time points. Altogether, this engineered streptavidin condensate platform provides a robust, rapid, and scalable approach for manipulating endogenous protein function under physiologically relevant conditions in both basic and translational research.

DOI: https://doi.org/10.64898/2026.05.22.725644
Nat Commun. 2026 Jun 05.

Programmable Nucleic Acid Sensing in Human Cells Using Circularizable ssDNA.

Ahmed Mahas, Raphael Ferreira, Lisa M Riedmayr, George M Church.

Programmable technologies that sense nucleic acid signatures in living cells and trigger cellular functions hold promise for biotechnology and medicine. Here, we develop SONAR (Sensing Of Nucleic acids using ASOs and Reverse-transcriptases), a platform that detects target DNA and RNA sequences and triggers controlled gene expression in human cells. SONAR operates through circularizable single-stranded DNA (ssDNA) sensors that, upon hybridization with complementary DNA or reverse-transcribed RNA, undergo target-dependent ligation via cellular ligases, subsequently driving expression of genetic payloads. For RNA sensing, we employ antisense oligonucleotides (ASOs) to prime targeted reverse transcription, generating complementary DNA that promotes ssDNA circularization. We demonstrate SONAR's ability to detect ssDNA, exogenous and endogenous RNA, couple sensing to programmable expression of diverse protein payloads, including reporters, recombinases, and genome editors, and enable enrichment and clonal recovery of target-positive cells from mixed populations. This platform establishes a versatile framework for targeted nucleic acid detection and inducible gene expression, with broad potential applications in diagnostics, therapeutics, and synthetic biology.

DOI: https://doi.org/10.1038/s41467-026-73990-5
Biofabrication. 2026 Jun 04.

Topology Optimization of 3D-Printed Mycelium Hydrogels.

Winston F Lindqwister, Mrinal Chaudhury, Sarah N Schyck, Iuri Rocha, Kunal Masania, Martin Lesueur.

  As we move towards more sustainable and resilient materials, new opportunities for harnessing the next generation of biological materials will arise. Materials composed of living organisms have great potential in fulfilling this role as a self-healing, lightweight and sustainable structural material. Recent advances in 3Dprinting using fungi-inoculated hydrogels opens the potential of additive manufacturing with fungi into optimized shapes. However, while this technique of 3D-printing fungi has great potential in a wide range of engineering applications, computational models do not yet exist to precisely engineer the strength of structures made from this material. Here we create a computational modeling scheme for 3D-printed mycelium structures, linking the growth of fungi to stiffness. We first model the growth of fungi through a diffusion model. We then convert the resultant density values into local stiffness, creating a computational representation of the varying elemental stiffness as a function of local mycelial density. We implement two Bayesian optimization-based topology optimization schemes to maximize the strength of cuboid 3D-printed structures while minimizing the input material cost. One maximizes the material specific stiffness while the other applies a constrained scheme for a identifying a minimized mass for a target design stiffness. Both show a distinct tradeoff in print mass to stiffness, with results validated experimentally. These new insights provide important next steps in the effective harnessing of this class of emergent material, as well as its larger adoption for engineering applications.

Keywords:  additive manufacturing; engineered living materials; fungi materials; hydrogel; mycelium; topology optimization

DOI:  https://doi.org/10.1088/1758-5090/ae7835
Adv Mater. 2026 Jun 01. e73573

Direct White-Light Reconfiguration of Dynamic Covalent Polymer Networks via Photoinsertable Spirothiopyran.

Shuailong Zhou, Mengqi Du, Zhaomiao Chu, Xuehan Yang, Chuang Li.

  Light offers a powerful, noninvasive tool for polymer reprocessing and recycling. However, existing strategies predominantly rely on high-energy ultraviolet (UV) irradiation, which often induces material degradation and compromises the integrity of dynamic covalent networks. Herein, we report a white-light-activated addition reaction between spirothiopyran (STP) and poly(disulfide) that enables the direct structural reconfiguration of polymer networks. Upon illumination (λ > 400 nm), STP isomerizes to its ring-opened thiomerocyanine (TMC) form, exposing a reactive ene moiety, while the poly(disulfide) backbone homolytically dissociates into sulfur-centered radicals. These intermediates undergo rapid thiol-ene coupling, establishing dynamic C-S linkages. Notably, this process operates efficiently within bulk poly(disulfide) matrices, allowing the direct incorporation of STP into the polymer backbone and subsequent topological rearrangement of the network. The resulting photoinsertion introduces additional crosslinks, which not only enhance the mechanical properties and photostability but also enable spatiotemporal control over material welding, adhesion, remolding, and recycling. Furthermore, the synergy between STP photochromism and spatially controlled photocrosslinking unlocks advanced functionalities such as dual-color encryption and biomimetic morphogenesis. This work establishes a sustainable, visible-light-driven platform for polymer reconfiguration and opens new avenues toward smart, adaptable functional materials.

Keywords:  dynamic covalent bond; photochromism; photoinsertion agent; photoswitch; poly(disulfide); spirothiopyran

DOI:  https://doi.org/10.1002/adma.73573
Nature. 2026 Jun;654(8117): 10

Why a synthetic human genome is still worth building.

Sudarshan Pinglay.



Keywords:  Bioinformatics; Biological techniques; Biotechnology; Genetics

DOI:  https://doi.org/10.1038/d41586-026-01725-z
Nat Commun. 2026 Jun 04.

ATP is dispensable for E. coli DNA replication and eukaryotic helicase activity.

Richard R Spinks, Aleksa Lakic, Celine Kelso, Slobodan Jergic, Olga Yurieva, Zhi-Qiang Xu, Michael E O'Donnell, Nicholas E Dixon, Antoine M van Oijen, Jacob S Lewis, Lisanne M Spenkelink.

Adenosine triphosphate (ATP) hydrolysis is the main cellular source of energy used to drive biochemical reactions that are otherwise energetically unfavourable. The chemical energy stored in phosphoanhydride bonds is released upon hydrolysis of ATP to ADP and is used to drive mechanical work and conformational change. DNA replication is a canonical process in which the multi-enzyme replisome is thought to rely on ATP hydrolysis for its function. Here we show, through single-molecule visualisation of DNA replication by the Escherichia coli replisome, that the replicative DnaB helicase does not rely on hydrolysis of ATP in the context of the elongating replisome. Even in the presence of physiologically-relevant concentrations of ATP, dTTP is hydrolysed preferably. Finally, we show that the replicative helicases from S. cerevisiae, D. melanogaster, and Homo sapiens can also use dTTP to unwind DNA. Our observations suggest that replicative helicases across domains of life are 'flex-fuel' helicases.

DOI: https://doi.org/10.1038/s41467-026-73893-5
Adv Mater. 2026 Jun 05. e21487

Silk-Based Protein Corona Enhances mRNA-LNP Vaccine Efficacy and Prevents Tumor Relapse.

Shangyuan Cui, Zhongfeng Ye, Mariah L Arral, Lihan Liu, Benson Weng, Xiaohan Zhang, Remya Nair, Yuchen Zhao, Jugal Kishore Sahoo, Shuliang Gao, Yushu Wang, Zhiyuan Qu, Zhongyang Shi, Qiaobing Xu, David L Kaplan.

  Lipid nanoparticles (LNPs) are clinically validated carriers for nucleic acid therapeutics; however, achieving targeted delivery to reticuloendothelial organs beyond the liver, lung, and spleen remains a major challenge. Here, we introduce a strategy for post-fabrication engineering of a custom protein corona on mRNA-LNPs using cationic silk fibroin (SF), a biocompatible and chemically tunable protein polymer. SF-coated LNPs exhibit enhanced cellular uptake and endosomal escape, resulting in a 3.6 fold increase in lymph node delivery and a 2.5 fold extension in in vivo protein expression compared to unmodified LNPs. In a cancer vaccine model, SF-LNPs significantly improve dendritic cell maturation, antigen cross-presentation, and cytotoxic T cell activation, leading to robust protection against tumor growth and metastasis, as well as durable immunological memory. This work expands the formulation space for LNPs and establishes silk fibroin as a modular surface engineering tool for enhancing the efficacy and specificity of mRNA-based therapeutics.

Keywords:  fifth component LNPs; lipid nanoparticles; lymph node‐targeting delivery; mRNA delivery; protein corona

DOI:  https://doi.org/10.1002/adma.202521487
bioRxiv. 2026 May 22. pii: 2026.05.21.726912. [Epub ahead of print]

High-throughput engineering of ligand-activated splicing ribozyme through domain insertion.

August Staubus, Ella Ramamurthy, Anika Gupta, Madison Furnish, Arjun Khakhar, James Chappell.

Domain insertion is an established method to engineer ligand-mediated control of activity in protein scaffolds. Whether this strategy can be systematically applied to large, structured RNAs remains unclear. In this study, we investigated the feasibility of engineering ligand-activated splicing ribozymes (LASRs) from group I catalytic introns. Using domain-insertion profiling coupled with high-throughput screening, we mapped the nucleotide-resolution landscape of aptamer insertion across the ribozyme and identified sites that support robust ligand-dependent control. We showed LASRs function across multiple kingdoms of life, including diverse species of bacteria and even fungi, and can be used to regulate various genetic outputs. Finally, we integrated LASRs with a genetic recorder that writes information into ribosomal RNA, enabling sequencing-based recovery of intracellular chemical signals from microbial consortia. This work establishes LASRs as an RNA-based inducible control platform for sensing diverse chemical inputs, regulating the expression of diverse genes of interest, and recording intracellular information.

DOI: https://doi.org/10.64898/2026.05.21.726912
ACS Nano. 2026 Jun 05.

Engineering Apical Integrin-Binding Cellular Patches to Direct Cell Reprogramming via Mechanical Remodeling.

Junchao Zhi, Tianrui Zhao, Wenjing Hou, Qizheng Zhang, Zhen Gao, Jiancan Yu, Kai Wu, Chenjie Xu, Xunwu Hu, Ye Zhang.

  Engineering extracellular microenvironments to control stem cell fate remains a central challenge in regenerative medicine. Here, we develop ECM-mimetic cellular patches formed by the supramolecular assembly of laminin-derived, integrin-binding ligands. The resulting fibrillar networks exhibit well-defined molecular packing and nanoscale ligand distribution, enabling specific engagement of apical integrin β1 on mesenchymal stem cells. This controlled interface converts molecular assembly into hierarchical mechanotransduction, coordinating cytoskeletal remodeling, nuclear deformation, and chromatin reorganization to drive neuronal reprogramming without genetic or chemical induction. Mechanistic studies reveal that the interplay between ligand assembly, spatial orientation, and network stability governs integrin activation and downstream transcriptional regulation. These findings demonstrate how molecularly programmed assemblies can transform passive matrices into active, cell-instructive materials. This work establishes a framework for designing supramolecular systems that couple structural hierarchy with mechanotransductive control to direct stem cell fate and advance regenerative material strategies.

Keywords:  cell reprogramming; cellular patches; integrin; mechanical remodeling; peptide assembly

DOI:  https://doi.org/10.1021/acsnano.6c04114
Curr Opin Chem Biol. 2026 Jun 04. pii: S1367-5931(26)00051-7. [Epub ahead of print]93 102702

Defining the rules of biocompatible chemistry.

Thomas W Thorpe, Stephen Wallace.

Biocompatible chemistry - the use of non-enzymatic, chemocatalytic reactions to interface with and manipulate cellular metabolism - has emerged as a powerful hybrid approach at the interface of synthetic chemistry and engineering biology. Early studies showed that abiotic catalysts can function in the presence of living cells and influence biological processes. More recent work demonstrates that such reactions can be integrated with native and engineered metabolism to access new chemical space, valorise waste feedstocks, and, in some cases, outperform conventional petrochemical processes from an environmental perspective. As the field matures, attention is shifting from proof-of-concept demonstrations to fundamental questions of mechanism: why some reactions are biocompatible, whether compatibility can be predicted or engineered, and where its limits lie. Addressing these questions, alongside defining practical boundaries, will be essential to realising the full potential of biocompatible chemistry in chemical biology, biotechnology, and sustainable manufacturing.

DOI: https://doi.org/10.1016/j.cbpa.2026.102702
bioRxiv. 2026 May 18. pii: 2026.05.16.725679. [Epub ahead of print]

Ratiometric transcriptional activation by protein degradation.

Melissa A Gray, Katelyn L Randal, Jennifer A Co, Michelle T Tang, Athena Z Xue, Sophia W Chen, Hlib Razumkov, Qusay Q Omran, David E Solow-Cordero, Jeonghye Yu, Stephanie A Robinson, Cara A Starnbach, Nathanael S Gray, Steven M Corsello, Steven M Banik.

Cells can respond to alterations in the abundances of specific proteins through transcriptional outputs. Synthetic approaches inspired by native post-transcriptional circuits that convert protein abundance changes into programmable gene expression would be transformative. Here, we discover and describe design principles that effectively convert protein degradation into transcriptional outputs in live cells. We define ratiometric transcriptional activation, where control over the ratio between a transcriptional inhibitor-protein of interest fusion and transcription factor enables detection of abundance changes with high sensitivity at scale. We show that ratiometric transcriptional activation can be implemented in single cells using triply orthogonal circuits or in multicellular pools, operating independently of mechanism of protein downregulation and enabling simultaneous detection of multiple protein downregulation events through outputs such as cell survival, fluorescent protein expression, or barcode sequencing. These circuits can be applied to oncogenic targets and enable discovery of new molecular glue degraders.

DOI: https://doi.org/10.64898/2026.05.16.725679
Nat Mater. 2026 Jun;25(6): 883

Tracking microstructure and mechanical response.

DOI: https://doi.org/10.1038/s41563-026-02633-3
Anal Chem. 2026 May 31.

In-Situ Metabolic Profiling of Single Living Cells by Liquid Secondary Ion Mass Spectrometry.

Yuxin Liu, Jilin Tang, Yifan Liang, Qun Luo, Bo Guan, Lirong Liang, Fuyi Wang, Yanyan Zhang.

Single-cell mass spectrometry enables label-free and high-throughput molecular analysis of individual cells. However, conventional vacuum-based secondary ion mass spectrometry (SIMS) faces challenges in probing metabolism of single living cells under native physiological conditions. Here, we introduce a liquid SIMS platform coupled with a vacuum-compatible cell-culture device, which allows in-situ metabolomic profiling of single living cells in their native culture environment without any pretreatment. This platform uniquely enables direct nanoscale interfacial characterization, and we report for the first time the determination, via MS depth profiling, of a lipid bilayer with a SiN-equivalent thickness of ∼8.6 nm in a single living human nonsmall cell lung cancer (A549) cell. As a proof of concept, we applied this method to investigate metabolomic changes linked to cisplatin resistance in A549 cells. Our findings indicate upregulation of cholesterol, phosphatidylcholine, and low-unsaturation fatty acids in resistant cells, and we demonstrate that inhibiting cholesterol synthesis effectively reduces drug resistance. This work underscores the potential of liquid SIMS for in-situ metabolic profiling during complex biological processes.

DOI: https://doi.org/10.1021/acs.analchem.6c00906
ACS Appl Mater Interfaces. 2026 Jun 06.

Decoupling Stiffness and Toughness in Solid Polymer Electrolytes via Reversible Crystallization.

Shuto Fujisawa, Kei Hashimoto, Ryota Tamate, Yuji Kamiyama, Kei Nishikawa, Yohei Miwa, Shoichi Kutsumizu, Takamasa Sakai, Koichi Mayumi.

  Solid polymer electrolytes (SPEs) are polymer-based, flexible, and nonflammable electrolytes, making them promising candidates for developing highly stretchable electrochemical devices. However, in conventional designs, toughness improvement is typically coupled with an increase in stiffness. This coupling often arises from the introduction of thermally reversible crystals (TRCs) of polymer, resulting in high stiffness, brittleness, and poor conformability to electrodes. In this study, we develop a material design strategy to decouple toughness from stiffness in SPEs using strain-induced crystallization (SIC) in a homogeneous four-branched poly(ethylene glycol) (Tetra-PEG) network. SIC significantly enhances the toughness without increasing the stiffness, enabling the formation of soft, tough, and stretchable SPEs. Building on this decoupled platform, stiffness was reintroduced through TRCs of PEG, yielding SPEs that were both stiff and highly fracture-resistant. Importantly, upon heating, these materials exhibited thermoplastic behavior, which improved their conformability to metal electrodes. Consequently, Li|Tetra-PEG SPE|Li symmetric cells exhibited reversible lithium plating and stripping with stable long-term cycling. Overall, the proposed design strategy effectively decouples toughness from stiffness, thereby overcoming the conventional trade-offs in SPEs.

Keywords:  X-ray scattering; battery; mechanical properties; sensor; solid polymer electrolyte; strain-induced crystallization

DOI:  https://doi.org/10.1021/acsami.6c05382
Annu Rev Virol. 2026 Jun 03.

Setting Boundaries: Surface Engineering of Viral-Inspired Materials.

Daniel de Castro Assumpção, Danielle Tullman-Ercek, Nolan W Kennedy.

Viral-inspired materials (VIMs) integrate the nanoscale precision of viral architecture with the versatility of synthetic modification, enabling interfaces that bridge biological and technological systems. This review outlines how surface engineering governs the structure-function relationship of VIMs, highlighting six core design strategies: natural viral surface utilization, genetic and chemical decoration, hybrid composite formation, geometric and dimensional control, stimuli-responsive materials, and hierarchical assembly. These approaches expand the material and functional diversity of viral scaffolds across biomedical, catalytic, and electronic applications. Emerging trends include developing unconventional protein architectures, de novo protein design, and hybrid material creation. Together, these developments position VIMs as powerful platforms for dynamic, programmable, and multifunctional materials that integrate biological precision and synthetic design.

DOI: https://doi.org/10.1146/annurev-virology-100424-102501
bioRxiv. 2026 May 19. pii: 2026.05.17.725791. [Epub ahead of print]

Nascent protein retention at polysomes reduces kinetic barriers to self-assembly.

Shriram Venkatesan, Alex Von Schulze, Jeffrey J Lange, Jacob Jensen, Lexie E Berkowicz, Dai Tsuchiya, Ning Zhang, Jennifer Gardner, Scott McCroskey, Ying Zhang, Selene Swanson, Yan Hao, Malcolm Cook, Tong Shu, Liam J Holt, Laurence Florens, Jay R Unruh, Randal Halfmann.

Living proteomes are necessarily far from equilibrium. It is paradoxical, then, that reducing the translation of new proteins -- which should promote equilibration -- instead prolongs life. We investigated the impact of translational flux to nucleation barriers that preserve the solubility of proteins destined to form amyloids or other assemblies. By manipulating translation initiation rates directly or indirectly, across yeast and human cells, and across a variety of supersaturable proteins, we find that accelerating translation initiation broadly accelerates nucleation irrespective of their global concentrations. We showed that this effect was confined to polysomes and was enhanced by N-terminal placement or other features that retained the nascent aggregating domain at polysomes. Finally, we show that intrinsically disordered regions with high tendencies to self-associate are specifically positioned to do so co-translationally, providing evidence that cotranslational nucleation has shaped proteome evolution.

DOI: https://doi.org/10.64898/2026.05.17.725791
Nat Protoc. 2026 Jun 04.

Label-free interferometry platform for drug response profiling of bioprinted tumor organoids at single-organoid resolution.

Bowen Wang, Peyton J Tebon, Thang L Nguyen, Graeme F Murray, Daniel C Guest, Jason Reed, Sara Sartini, Alice Soragni, Michael A Teitell.

Organoids have become mainstay tools for drug discovery and personalized medicine. High-throughput imaging readouts for drug screening of tumor organoids are of particular interest as organoid-level quantification of responses provides insights into heterogeneity, which is relevant for predicting therapeutic efficacy and anticipating emergence of resistance. However, screening extracellular matrix (ECM)-embedded organoids remains technically challenging. Standard methods with manual cell seeding in thick ECM constructs impede imaging efficiency, whereas bulk endpoint assays are easy to implement but fail to resolve single-organoid-level drug response data. Here we present a protocol to bioprint cells within a temperature-sensitive ECM in thin, flat, square-shaped patterns in 96-well plates to establish three-dimensional (3D) cultures for efficient, high-throughput, time-resolved quantitative phase imaging at single-organoid resolution. Quantitative phase imaging of 3D-bioprinted organoids using high-speed live cell interferometry coupled with machine learning analyses enables label-free quantification of biomass, growth kinetics and drug response profiles of thousands of individual organoids per experiment. We demonstrate that the protocol can be leveraged to automatically generate plates containing thousands of organoids for high-throughput imaging and drug screening experiments, quantify growth and drug response heterogeneity, resolve rare phenotypes and identify predictive features of drug response profiles for fundamental studies and therapeutic decision-making. This protocol can be completed in 2 weeks or less and can be adapted to organoids derived from a variety of cell sources and to alternative screening paradigms. The protocol requires familiarity with coding and experience with 3D cell culture, optical assembly and software installation.

DOI: https://doi.org/10.1038/s41596-026-01375-5
ACS Appl Mater Interfaces. 2026 Jun 05.

Engineered Cellulose Nanofiber/SiC Nanowire Films via Combustion Synthesis and Alignment for High-Performance Flexible Thermal Management.

Yutong Dai, Lei Zhao, Yinuo Ma, Zhilei Wei, Hongyan Xia, Zhongqi Shi.

  The pursuit of high-performance, flexible thermal interface materials (TIMs) is hindered by the difficulty in simultaneously achieving efficient filler production, uniform dispersion, and multifunctional synergy in polymer composites. To address this, we presented an integrated engineering strategy that combined rapid combustion synthesis, a tailored dispersion pretreatment, vacuum-assisted alignment, and interfacial hydrogen-bonding design. Specifically, high-aspect-ratio silicon carbide nanowires (SiCNWs) were rapidly synthesized via combustion synthesis. A combined crushing-ball milling-rotary evaporation process effectively improved their dispersibility, after which they were aligned in-plane within a cellulose nanofiber (CNF) matrix through vacuum filtration. Effective interfacial adhesion was achieved via hydrogen bonding between the surface oxide layer of SiCNWs and the CNF. The resulting composite with 40 wt % SiCNWs exhibited an in-plane thermal conductivity of 22.3 W·m-1·K-1 (a 20-fold enhancement over pure CNF) and a tensile strength of 93 MPa, while retaining excellent electrical insulation (>109 Ω·cm) and thermal stability. These exceptional properties arose synergistically from the aligned conductive network and the hydrogen-bond-enhanced interface, which facilitated phonon transport and stress transfer concurrently. This work not only demonstrates high-performance flexible TIMs but also provides a facile and practical route for fabricating multifunctional composites for next-generation electronic thermal management.

Keywords:  cellulose nanofiber; combustion synthesis; flexible electronics; silicon carbide nanowires; thermal interface materials

DOI:  https://doi.org/10.1021/acsami.6c02816
ACS Biomater Sci Eng. 2026 Jun 01.

Engineering a GelMA Hydrogel-Based Biomimetic Endometrium-on-a-Chip for Studying Embryo Implantation.

Zhenxing Shi, Juan Liu, Ziyi Ouyang, Lei Guo, Shuyan Wang, Binyang Du, Dan Zhang, Huiquan Wang.

  Recurrent implantation failure is a critical bottleneck that limits the clinical success rates of assisted reproductive technologies. Existing in vitro implantation models often struggle to balance the conflicting needs of "fluid supply" and "embryo protection": static models lack necessary hydrodynamic stimulation, whereas traditional microfluidic perfusion frequently causes blastocyst damage due to excessive shear stress. Furthermore, most existing scaffold materials fail to mimic the critical dynamic mechanical remodeling of the endometrium during the implantation window. To overcome these limitations, this study constructed a biomimetic endometrium-on-a-chip based on methacryloyl gelatin (GelMA) hydrogels and micropillar arrays, aiming to reconstruct an implantation mechanical microenvironment that closely mimics in vivo conditions. In terms of engineering design, we optimized the micropillar array structure via COMSOL Multiphysics simulation to achieve spatial decoupling of shear stress. This design created a "mechanical sanctuary" for the embryo with shear stress lower than 0.3 dyn/cm2, effectively preventing fluid shear-induced damage while ensuring dynamic nutrient exchange. Regarding the material strategy, this study revealed the concentration-dependent degradation kinetics of GelMA hydrogels. Leveraging their "fast-then-slow" degradation behavior, we recapitulated the mechanical transition of the endometrium, aligning our matrix's softening profile with the physiological shift toward the receptive state characteristic of the implantation window. Biological experiments demonstrated that the GelMA-based hydrogel significantly enhanced the adhesion and zona hatching rates of mouse blastocysts compared to traditional static cultures. Furthermore, by integrating this biomimetic scaffold into a dynamically perfused microfluidic platform, we successfully established a robust in vitro model of mouse embryo implantation.

Keywords:  GelMA hydrogel; dynamic stiffness remodeling; embryo implantation; endometrium-on-a-chip; shear-stress shielding

DOI:  https://doi.org/10.1021/acsbiomaterials.6c00337
Sci Adv. 2026 Jun 05. 12(23): eaed9514

Bioinspired spatiotemporal control of microhelix formation and actuation.

Xin Hu, Benjamin R Greenvall, Eric Chia, Zhaojie Zhang, Stephen S Nonnenmann, Alfred J Crosby.

Helical structures provide critical functions in structural stability, locomotion, and mechanical flexibility. Among the helical structures, the dynamic coiled tendril formation in climbing plants upon contact with support structures inspires the development of numerous helix-based actuators and soft robotics. However, achieving precise spatiotemporal control over helix formation and actuation at the microscale remains a challenge. We introduce a materials system in which the spatial location and dynamics of helix formation are governed by the intrinsic bending resulting from the differential swelling of polyacrylic acid copolymer hydrogels, with electric fields serving as the primary control for electroosmotic flow-induced swelling/deswelling phase transitions. By manipulating electric field polarity and using patterned substrates, we achieve reversible spatiotemporal control over helix formation and actuation. The swelling/deswelling mechanism enables the applications of rotary actuation and controlled microsphere capture-release. Our approach represents a notable advancement in the precise dynamical control of helix formation, opening avenues for the development of sophisticated microactuators and artificial muscle systems.

DOI: https://doi.org/10.1126/sciadv.aed9514
Nat Chem Biol. 2026 Jun 03.

Achieving cell-type-specific bioorthogonal chemistry using enzyme-activated caged tetrazines.

Caroline H Knittel, Stormi R Chadwick, Jacob A Vance, Cedrik Kuehling, Neal K Devaraj.

Bioorthogonal reactions have revolutionized molecular biology through the conjugation of molecules within cellular environments. However, classical bioorthogonal reagents often suffer from nonspecific reactivity across diverse physiological contexts, diminishing their precision. This limitation presents considerable challenges in complex biological systems where multiple cell types coexist. Here we demonstrate tetrazine release and activation by cellular enzymes (TRACE), a method enabling cell-type-specific bioorthogonal chemistry. TRACE uses caged dihydrotetrazine derivatives, which remain inert until activated by specific cellular enzymes. Optimizing the electronic properties of the dihydrotetrazine scaffold enables rapid uncaging and activation of tetrazines within minutes. We demonstrate the utility of TRACE for the targeted release of cytotoxic drugs, selectively impacting the viability of enzyme-expressing cells in cocultures. Additionally, our method facilitates the delivery of imaging agents to subcellular structures in an enzyme-activity-dependent manner. TRACE represents a promising approach for programmable bioorthogonal chemistry in therapeutic and imaging applications.

DOI: https://doi.org/10.1038/s41589-026-02240-y