bims-enlima 2025-04-13 papers

bims-enlima

Biomed News

on Engineered living materials

Issue of 2025–04–13
twenty-six papers selected by
Rahul Kumar, Tallinna Tehnikaülikool

Emerging supramolecular and living materials in oral medicine.
Spatiotemporal dynamic and catalytically mediated reconfiguration of compartmentalized cyanuric acid/polyadenine DNA microdroplet condensates.
DNA-Based Signal Circuit for Self-Regulated Bidirectional Communication in Protocell-Living Cell Communities.
De novo design of inducibly assembling multi-component filaments.
Light-Based Juxtacrine Signaling Between Synthetic Cells.
Noninvasive and in situ identification of the phenotypes and differentiation stages of individual living cells entrapped within hydrogels.
Generation of an inflammatory niche in a hydrogel depot through recruitment of key immune cells improves efficacy of mRNA vaccines.
Hyperspectral reporters for long-distance and wide-area detection of gene expression in living bacteria.
DNA photofluids show life-like motion.
Genomically recoded organisms: redefining and safeguarding biological systems.
Multifunctional dithiolane monomers for multi-scale, recyclable light-driven additive manufacturing.
Firefly-Inspired 3D Printable Multi-Stimuli-Responsive Fluorescent Hydrogels with Adaptive Luminescence.
Hierarchical Self-Assembly of Magnetic Handshake Materials.
Library-based single-cell analysis of CAR signaling reveals drivers of in vivo persistence.
Macroscale-area patterning of three-dimensional DNA-programmable frameworks.
Design and Functionality of Trypsin-Triggered, Expandable Bovine Serum Albumin-Polyethylene Glycol Diacrylate Hydrogel Actuators.
Multi-material Gradient Printing Using Meniscus-enabled Projection Stereolithography (MAPS).
Massive Transfer and Assembly of Microscale Superlubric Materials.
A cofactor mediated supramolecular oligo-adenine triplex for reprogrammable macroscopic hydrogel assembly.
Engineering Conductive Hydrogels with Tissue-like Properties: A 3D Bioprinting and Enzymatic Polymerization Approach.
Chemically active wetting.
Designing for degradation: the importance of considering biotic and abiotic polymer degradation.
Mutualism breakdown underpins evolutionary rescue in an obligate cross-feeding bacterial consortium.
Reprogramming site-specific retrotransposon activity to new DNA sites.
Cellulose Gels: Functional Design and Promising Smart Applications.
Extracellular respiration is a latent energy metabolism in Escherichia coli.

Trends Biotechnol. 2025 Apr 07. pii: S0167-7799(25)00091-5. [Epub ahead of print]

Emerging supramolecular and living materials in oral medicine.

Nicholas G Fischer, Tsung-Yi Lin, Yuanhui Xiang, Ting Sang, Zhou Ye.

  Conventional dental materials lack the ability to promote regeneration, necessitating innovative approaches for repairing dental, oral, and craniofacial (DOC) tissues. Supramolecular materials with reversible, tunable interactions, and engineered living materials (ELMs) that mimic natural tissue dynamics, present a promising pathway towards regenerative solutions in oral medicine. This review introduces the potential of these biomaterials, focusing on their applications in oral bioprinting, therapeutic delivery, and organ-on-a-chip (OOC) systems. We discuss the integration of these technologies into clinical applications, and offer insights into future developments that may redefine oral healthcare by enabling the regeneration of complex, dynamic tissue structures and improving therapeutic outcomes in oral diseases.

Keywords:  bioprinting; drug delivery; living materials; organ-on-a-chip; supramolecular materials

DOI:  https://doi.org/10.1016/j.tibtech.2025.03.006
Nat Commun. 2025 Apr 09. 16(1): 3352

Spatiotemporal dynamic and catalytically mediated reconfiguration of compartmentalized cyanuric acid/polyadenine DNA microdroplet condensates.

Shijun Xu, Yu Ouyang, Yunlong Qin, Danlong Chen, Zhijuan Duan, Dongxing Song, Daniel Harries, Fan Xia, Itamar Willner, Fujian Huang.

Native cells possess membrane-bound subcompartments, organelles, such as mitochondria and lysosomes, that intercommunicate and regulate cellular functions. Extensive efforts are directed to develop synthetic cells, or protocells, that replicate these structures and functions. Among these approaches, phase-separated coacervate microdroplets composed of polymers, polysaccharides, proteins, or nucleic acids are gaining interest as cell-mimicking systems. Particularly, compartmentalization of the synthetic protocell assemblies and the integration of functional constituents in the containments allowing signaling, programmed transfer of chemical agents, and spatiotemporal controlled catalytic transformations across the protocell subdomains, are challenging goals in developing artificial cells. Here, we report the assembly of compartmentalized, phase-separated cyanuric acid/polyadenine coacervate microdroplets. Hierarchical, co-centric compartmentalization is achieved through the dynamic and competitive spatiotemporal occupation of pre-engineered barcode domains within the polyadenine microdroplet framework by invading DNA strands. By encoding structural and functional information within these DNA-invaded compartments, the light-triggered, switchable reconfiguration of compartments, switchable catalytic reconfiguration of containments, and reversible aggregation/deaggregation of the compartmentalized microdroplets are demonstrated.

DOI: https://doi.org/10.1038/s41467-025-58650-4
Angew Chem Int Ed Engl. 2025 Apr 07. e202503903

DNA-Based Signal Circuit for Self-Regulated Bidirectional Communication in Protocell-Living Cell Communities.

Lexun Li, Shuang Liu, Chundi Zhu, Shuxuan Shao, Fan Yang, Qiaoling Liu, Weihong Tan.

  Developing synthetic biology tools to control cell-to-cell signaling can provide new capabilities to engineer cell-cell communication and program desired cellular behaviors. As cell mimics, abiotic protocells provide an attractive opportunity to modulate the intercellular communication with design-based regulatory features. Despite the chemical communication of protocells that interact with living cells have been demonstrated, the autonomous regulation of intercellular signal transmission in protocell/living cell community remains a critical challenge. Herein, we designed a DNA circuit consisting of a recognition module, activation module, and feedback module that enables protocells to self-regulate the interaction with living cells by sensing and responding to the signal released from living cells. The feedback module with renewable capability is capable of processing the signal transduction on the membrane surface of protocells and controlling intercellular adhesion. Once dissociated from living cells, the disengaged protocells allow the following interaction with multiple target living cells in succession. Overall, this work provides an avenue to control and program dynamic signal propagation in protocell/living cell community. The designed communication with living cells would open new ways to tune cellular behavior and apply them to cell-based therapeutics.

Keywords:  DNA circuit; DNA nanotechnology; intercellular communication; protocell; self-regulation

DOI:  https://doi.org/10.1002/anie.202503903
bioRxiv. 2025 Mar 26. pii: 2025.03.26.645066. [Epub ahead of print]

De novo design of inducibly assembling multi-component filaments.

Hao Shen, Eric M Lynch, Noel Jameson, Justin Decarreau, Chenyang Shi, Zibo Chen, William Sheffler, Miaomiao Xu, James J De Yoreo, Jesse G Zalatan, Justin M Kollman, David Baker.

The design of multi-component nanomaterials is an outstanding challenge. Here, we describe the computational design of protein filaments with two or three distinct structural components that assemble into micron-scale, well-ordered fibers when mixed. CryoEM structure determination of four fiber designs was close to the computational design models. Filament assembly can be initiated by mixing the components, and modulated by addition and/or phosphorylation of designed regulatory subunits. This work demonstrates that regulatable multi-component protein filament systems can now be designed, opening the door to a wide range of engineered materials.

DOI: https://doi.org/10.1101/2025.03.26.645066
Small Sci. 2025 Jan;5(1): 2400401

Light-Based Juxtacrine Signaling Between Synthetic Cells.

Hossein Moghimianavval, Kyle J Loi, Sung-Won Hwang, Yashar Bashirzadeh, Allen P Liu.

  Cell signaling through direct physical cell-cell contacts plays vital roles in biology during development, angiogenesis, and immune response. Intercellular communication mechanisms between synthetic cells constructed from the bottom up are majorly reliant on diffusible chemical signals, thus limiting the range of responses in receiver cells. Engineering contact-dependent signaling between synthetic cells promises to unlock more complicated signaling schemes with spatial responses. Herein, a light-activated contact-dependent communication scheme for synthetic cells is designed and demonstrated. A split luminescent protein is utilized to limit signal generation exclusively to contact interfaces of synthetic cells, driving the recruitment of a photoswitchable protein in receiver cells, akin to juxtacrine signaling in living cells. The modular design not only demonstrates contact-dependent communication between synthetic cells but also provides a platform for engineering orthogonal contact-dependent signaling mechanisms.

Keywords:  Nanoluc Binary Technology (NanoBiT); SpyTag–SpyCatcher; juxtacrine signalings; light‐induced dimerizing proteins (iLIDs)–SspB; synthetic cell communications; synthetic cells

DOI:  https://doi.org/10.1002/smsc.202400401
Analyst. 2025 Apr 08.

Noninvasive and in situ identification of the phenotypes and differentiation stages of individual living cells entrapped within hydrogels.

Isamar Pastrana-Otero, Apurva R Godbole, Mary L Kraft.

Microscale screening platforms that allow cells to interact in three dimensions (3D) with their microenviroment have been developed as a tool for identifying the extrinsic cues that might stimulate stem cells to replicate without differentiating within artificial cultures. Though these platforms reduce the number of valuable stem cells that must be used for screening, analyzing the fate decisions of cells in these platforms can be challenging. New noninvasive approaches for identifying the lineage-specific differentiation stages of cells while they are entrapped in the hydrogels used for these 3D cultures are especially needed. Here we used Raman spectra acquired from individual, living cells entrapped within a hydrogel matrix and multivariate analysis to identify cell phenotype noninvasively and in situ. We collected a single Raman spectrum from each cell of interest while it was entrapped within a hydrogel matrix and used partial least-squares discriminant analysis (PLS-DA) of the spectra for cell phenotype identification. We first demonstrate that this approach enables identifying the lineages of individual, living cells from different laboratory lines entrapped within two different hydrogels that are used for 3D culture, collagen and gelatin methacrylate (gelMA). Then we use a hematopoietic progenitor cell line that differentiates into different types of macrophages to show that the lineage-specific differentiation stages of individual, living hematopoietic cells entrapped inside of gelMA scaffolds may be identified by PLS-DA of Raman spectra. This ability to noninvasively identify the lineage-specific differentiation stages of cells without removing them from a 3D culture could enable tracking the differentiation of the same cell over time.

DOI: https://doi.org/10.1039/d4an00800f
Sci Adv. 2025 Apr 11. 11(15): eadr2631

Generation of an inflammatory niche in a hydrogel depot through recruitment of key immune cells improves efficacy of mRNA vaccines.

Emily L Meany, John H Klich, Carolyn K Jons, Tianyang Mao, Namit Chaudhary, Ashley Utz, Julie Baillet, Ye E Song, Olivia M Saouaf, Ben S Ou, Shoshana C Williams, Noah Eckman, Darrell J Irvine, Eric Appel.

Messenger RNA (mRNA) delivered in lipid nanoparticles (LNPs) rose to the forefront of vaccine candidates during the COVID-19 pandemic due to scalability, adaptability, and potency. Yet, there remain critical areas for improvements of these vaccines in durability and breadth of humoral responses. In this work, we explore a modular strategy to target mRNA/LNPs to antigen-presenting cells with an injectable polymer-nanoparticle (PNP) hydrogel technology, which recruits key immune cells and forms an immunological niche in vivo. We characterize this niche on a single-cell level and find it is highly tunable through incorporation of adjuvants like MPLAs and 3M-052. Delivering commercially available severe acute respiratory syndrome coronavirus 2 mRNA vaccines in PNP hydrogels improves the durability and quality of germinal center reactions, and the magnitude, breadth, and durability of humoral responses. The tunable immune niche formed within PNP hydrogels effectively skews immune responses based on encapsulated adjuvants, creating opportunities to precisely modulate mRNA/LNP vaccines for various indications from infectious diseases to cancers.

DOI: https://doi.org/10.1126/sciadv.adr2631
Nat Biotechnol. 2025 Apr 11.

Hyperspectral reporters for long-distance and wide-area detection of gene expression in living bacteria.

Yonatan Chemla, Itai Levin, Yueyang Fan, Anna A Johnson, Connor W Coley, Christopher A Voigt.

Genetically encoded reporters are suitable for short-distance imaging in the laboratory but not for scanning wide outdoor areas from a distance. Here we introduce hyperspectral reporters (HSRs) designed for hyperspectral imaging cameras that are commonly mounted on unmanned aerial vehicles and satellites. HSR genes encode enzymes that produce a molecule with a unique absorption signature that can be reliably distinguished in hyperspectral images. Quantum mechanical simulations of 20,170 metabolites identified candidate HSRs, leading to the selection of biliverdin IXα and bacteriochlorophyll a for their distinct absorption spectra and biosynthetic feasibility. These genes were integrated into chemical sensor circuits in soil (Pseudomonas putida) and aquatic (Rubrivivax gelatinosus) bacteria. The bacteria were detectable outdoors under ambient light from up to 90 m in a single 4,000-m2 hyperspectral image taken using fixed and unmanned aerial vehicle-mounted cameras. The dose-response functions of the chemical sensors were measured remotely. HSRs enable large-scale studies and applications in ecology, agriculture, environmental monitoring, forensics and defense.

DOI: https://doi.org/10.1038/s41587-025-02622-y
Nat Mater. 2025 Apr 09.

DNA photofluids show life-like motion.

Qi-Hong Zhao, Jin-Ying Qi, Nan-Nan Deng.

As active matter, cells exhibit non-equilibrium structures and behaviours such as reconfiguration, motility and division. These capabilities arise from the collective action of biomolecular machines continuously converting photoenergy or chemical energy into mechanical energy. Constructing similar dynamic processes in vitro presents opportunities for developing life-like intelligent soft materials. Here we report an active fluid formed from the liquid-liquid phase separation of photoresponsive DNA nanomachines. The photofluids can orchestrate and amplify nanoscale mechanical movements by orders of magnitude to produce macroscopic cell-like behaviours including elongation, division and rotation. We identify two dissipative processes in the DNA droplets, photoalignment and photofibrillation, which are crucial for harnessing stochastic molecular motions cooperatively. Our results demonstrate an active liquid molecular system that consumes photoenergy to create ordered out-of-equilibrium structures and behaviours. This system may help elucidate the physical principles underlying cooperative motion in active matter and pave the way for developing programmable interactive materials.

DOI: https://doi.org/10.1038/s41563-025-02202-0
Trends Biotechnol. 2025 Apr 03. pii: S0167-7799(25)00121-0. [Epub ahead of print]

Genomically recoded organisms: redefining and safeguarding biological systems.

Miriam Amiram.

  In a recent report, Grome et al. describe a genomically recoded Escherichia coli strain with a 62-codon genome and a single stop codon. This and other genomically recoded organisms (GROs), engineered with modified genetic vocabularies, enable the creation of novel proteins and biomaterials, while ensuring the safety and viability of GRO-based biomanufacturing.

Keywords:  biocontainment; genomically recoded organisms; noncanonical amino acids; orthogonal translation machinery

DOI:  https://doi.org/10.1016/j.tibtech.2025.03.014
Polym Chem. 2025 Apr 02.

Multifunctional dithiolane monomers for multi-scale, recyclable light-driven additive manufacturing.

Benjamin R Nelson, Jaxon T Cione, Bruce E Kirkpatrick, Kendra M Kreienbrink, Abhishek P Dhand, Jason A Burdick, C Wyatt Shields Iv, Kristi S Anseth, Christopher N Bowman.

In this work, we develop a tetrafunctional monomer incorporating 1,2-dithiolanes as the reactive group, lipoic acid pentaerythritol ethoxylate, which is capable of photopolymerization and is suitable for light-based additive manufacturing with high spatial resolution across various length scales. This monomer polymerizes in either the presence or absence of exogenous photoinitiator. Using dynamic light processing and two photon lithography techniques, parts were printed on size scales ranging from multiple cm to μm, with resolution as small as 1 μm. As a result of the dithiolane polymerization, linear disulfides are formed, forming covalent adaptable networks directly from the polymerization reaction. Furthermore, through heating and dilution in solvent, the network was recycled back to the lipoic acid functional monomer with approximately 95% monomer recovery, which was subsequently repolymerized to achieve nearly identical modulus evolution as a function of exposure time. This work represents an advance in the development of multifunctional dithiolane monomers, as well as recyclable resins for additive manufacturing that are capable of polymerization with or without exogenous photoinitiators.

DOI: https://doi.org/10.1039/d5py00199d
ACS Nano. 2025 Apr 10.

Firefly-Inspired 3D Printable Multi-Stimuli-Responsive Fluorescent Hydrogels with Adaptive Luminescence.

Diwei Shi, Donghwan Ji, Xiao Li, Zhecun Guan, Minghao Li, Jinhye Bae.

  Bioluminescent organisms, such as fireflies, jellyfish, and glow worms, possess a superb capacity for environment-interactive luminescence, enabling them to adapt to their surroundings. However, developing artificial luminescent materials that mimic the wet, soft, flexible, and multistimuli-responsive nature of bioluminescent organisms remains a challenge. Here, we present a rational design strategy for multistimuli-responsive fluorescent hydrogels in diverse and complex shapes, mimicking the bioluminescent behavior of fireflies. The fluorescence is activated and enhanced by natural and sustainable stimuli─water and temperature─and can be reversibly deactivated on-demand, similar to the role of oxygen and temperature in the firefly bioluminescence. Specifically, the designed molecular additives integrated within the hydrogel matrix increase fluorescence intensity and enhance the reversible and repetitive responsiveness to surrounding solvents without diminishing fluorescence intensity. Moreover, the hydrogel matrix responding to temperature changes enables control of fluorescence. Furthermore, the hydrogel precursor, designed for good printability, allows 3D printing of diverse-shaped fluorescent hydrogel structures, including artificial fluorescent organism models and fluorescence-patterned displays. This capability extends to implementing on-demand dynamic information encryption-decryption display with controllable fluorescent intensity and on-off rates. The proposed design strategy and free-form fabrication of fluorescent hydrogels could provide a viable path toward advanced fluorescent hydrogel development.

Keywords:  3D printing; biomimicking; fluorescent hydrogels; information encryption; multistimuli responsiveness

DOI:  https://doi.org/10.1021/acsnano.4c15111
ACS Nano. 2025 Apr 11.

Hierarchical Self-Assembly of Magnetic Handshake Materials.

Andreia L Fenley, Chrisy Xiyu Du, Paul L McEuen, Itai Cohen, Michael P Brenner, Julia Dshemuchadse.

  Through programmable self-assembly, simple building blocks can be made to form highly complex structures following local rules of interaction. However, materials systems that are most commonly utilized for programmable assembly often lack interactions that exhibit the strength, specificity, and long ranges, which would, as a result, allow for robust and rapid hierarchical self-assembly processes. "Magnetic handshake" building blocks resolve many of these challenges at once, incorporating strong, long-range, and specific magnetic interactions through patterning of magnetic dipoles onto rigid panels. When appropriately designed, the panels organize hierarchically: first into chains, and subsequently those chains combine to form dense stacks. Here, we examine differences in phase behavior and morphology for four panel types. We delineate how perpendicular chaining and stacking interactions between panels compete and how they can be manipulated to reverse the sequence of the hierarchical assembly pathway. Collectively, our work shows the enormous potential for using magnetic handshake materials for self-assembly of hierarchically organized complex structures.

Keywords:  hierarchical structure; magnetic metamaterials; molecular dynamics; phase behavior; self-assembly

DOI:  https://doi.org/10.1021/acsnano.4c16484
Cell Syst. 2025 Apr 09. pii: S2405-4712(25)00093-6. [Epub ahead of print] 101260

Library-based single-cell analysis of CAR signaling reveals drivers of in vivo persistence.

Caleb R Perez, Andrea Garmilla, Avlant Nilsson, Hratch M Baghdassarian, Khloe S Gordon, Louise G Lima, Blake E Smith, Marcela V Maus, Douglas A Lauffenburger, Michael E Birnbaum.

  The anti-tumor function of engineered T cells expressing chimeric antigen receptors (CARs) is dependent on signals transduced through intracellular signaling domains (ICDs). Different ICDs are known to drive distinct phenotypes, but systematic investigations into how ICD architectures direct T cell function-particularly at the molecular level-are lacking. Here, we use single-cell sequencing to map diverse signaling inputs to transcriptional outputs, focusing on a defined library of clinically relevant ICD architectures. Informed by these observations, we functionally characterize transcriptionally distinct ICD variants across various contexts to build comprehensive maps from ICD composition to phenotypic output. We identify a unique tonic signaling signature associated with a subset of ICD architectures that drives durable in vivo persistence and efficacy in liquid, but not solid, tumors. Our findings work toward decoding CAR signaling design principles, with implications for the rational design of next-generation ICD architectures optimized for in vivo function.

Keywords:  CAR T cells; T cell signaling; T cells; chimeric antigen receptors; immunotherapy; intracellular signaling domains; persistence; pooled screens; single-cell RNA sequencing; tonic signaling

DOI:  https://doi.org/10.1016/j.cels.2025.101260
Nat Commun. 2025 Apr 04. 16(1): 3238

Macroscale-area patterning of three-dimensional DNA-programmable frameworks.

Feiyue Teng, Honghu Zhang, Dmytro Nykypanchuk, Ruipeng Li, Lin Yang, Nikhil Tiwale, Zhaoyi Xi, Mingzhao Liu, Mingxin He, Shuai Zhang, Oleg Gang.

DNA, owing to its adaptable structure and sequence-prescribed interactions, provides a versatile molecular tool to program the assembly of organized three-dimensional (3D) nanostructures with precisely incorporated inorganic and biomolecular nanoscale components. While such programmability allows for self-assembly of lattices with diverse symmetries, there is an increasing need to integrate them onto planar substrates for their translation into applications. In this study, we develop an approach for the growth of 3D DNA-programmable frameworks on arbitrarily patterned silicon wafers and metal oxide surfaces, as well as study the leading effects controlling these processes. We achieve the selective growth of DNA origami superlattices into customized surface patterns with feature sizes in the tens of microns across macroscale areas using polymer templates patterned by electron-beam lithography. We uncover the correlation between assembly conditions and superlattice orientations on surfaces, lattice domain sizes, twining, and surface coverage. The demonstrated approach opens possibilities for bridging self-assembly with traditional top-down nanofabrication for creating engineered 3D nanoscale materials over macroscopic areas with nano- and micro-scale controls.

DOI: https://doi.org/10.1038/s41467-025-58422-0
Small Sci. 2024 Oct;4(10): 2400214

Design and Functionality of Trypsin-Triggered, Expandable Bovine Serum Albumin-Polyethylene Glycol Diacrylate Hydrogel Actuators.

Yuchen Liu, Luai R Khoury.

  Expandable shape-morphing hydrogels that ensure prolonged site residence, have tailored mechanical integrity and tunability, are biocompatible to minimize side effects and can release drugs over an extended time remain challenging to achieve. Herein, a new class of enzyme-triggered bovine serum albumin and polyethylene glycol diacrylate hybrid hydrogels is presented, contributing to advancements in controlled drug-model release and actuation. These hydrogels combine the intrinsic properties of proteins with the resilience of synthetic polymers, offering a versatile application platform. Central to our research is the trypsin-induced simultaneous functionality of controlled drug model release and dynamic shape changes under physiological trypsin concentrations (0.01% w/v). These hydrogels display tailored mechanical and physical properties and microstructure, which are crucial for biomedical devices, soft robotics, and tissue engineering applications. Additionally, the hydrogels effectively control the release of fluorescein isothiocyanate, a model drug, indicating their potential for highly targeted drug delivery, particularly in the gastrointestinal tract. The study also highlights the significant effect of shape-morphing on drug release rates under physiological trypsin concentrations. These findings suggest that enzyme-responsive hybrid protein-polymer hydrogel actuators with tailored mechanical and physical properties can enhance the precision of drug delivery in biomedical applications.

Keywords:   protein‐based materials; albumin; controlled drug release; polyethylene glycol diacrylate; soft actuators

DOI:  https://doi.org/10.1002/smsc.202400214
Adv Mater Technol. 2025 Mar 18. pii: 2400675. [Epub ahead of print]10(6):

Multi-material Gradient Printing Using Meniscus-enabled Projection Stereolithography (MAPS).

Puskal Kunwar, Arun Poudel, Ujjwal Aryal, Rui Xie, Zachary J Geffert, Haven Wittmann, Daniel Fougnier, Tsung Hsing Chiang, Mathew M Maye, Zhen Li, Pranav Soman.

  Light-based additive manufacturing methods have been widely used to print high-resolution 3D structures for applications in tissue engineering, soft robotics, photonics, and microfluidics, among others. Despite this progress, multi-material printing with these methods remains challenging due to constraints associated with hardware modifications, control systems, cross-contamination, waste, and resin properties. Here, we report a new printing platform coined Meniscus-enabled Projection Stereolithography (MAPS), a vat-free method that relies on generating and maintaining a resin meniscus between a crosslinked structure and bottom window to print lateral, vertical, discrete, or gradient multi-material 3D structures with no waste and user-defined mixing between layers. We show that MAPS is compatible with a wide range of resins and can print complex multi-material 3D structures without requiring specialized hardware, software, or complex washing protocols. MAPS's ability to print structures with microscale variations in mechanical stiffness, opacity, surface energy, cell densities, and magnetic properties provides a generic method to make advanced materials for a broad range of applications.

Keywords:  bioprinting; digital light processing; gradient printing; meniscus; multi-material printing; nano-material printing

DOI:  https://doi.org/10.1002/admt.202400675
ACS Appl Mater Interfaces. 2025 Apr 09.

Massive Transfer and Assembly of Microscale Superlubric Materials.

Dinglin Yang, Miaoxuan Xue, Minhao Han, Yelingyi Wang, Ziqin Jiang, Quanshui Zheng, Deli Peng.

  Structural superlubricity (SSL) offers a revolutionary solution to the challenges of friction and wear. However, current transfer methods for superlubric materials rely on probe-based techniques that are limited to individual, one-by-one transfers. Moreover, the maximum achievable scale of SSL is constrained by the single-crystal size and defect distribution of the material. To enable the mass production of devices and the scaling of SSL contact areas, scalable transfer and assembly techniques are critically needed. Here, we introduce a batch "slide-and-lift" dry transfer technique that leverages the sliding motion of polydimethylsiloxane stamps to modulate adhesion at van der Waals interfaces, enabling the simultaneous transfer of hundreds of sliders. This technique accommodates sliders of various sizes and shapes while ensuring their surfaces remain ultraclean and defect-free. Transferred slider arrays are successfully released onto various substrates, maintaining their superlubric properties. Furthermore, these transferred sliders are assembled to achieve larger-scale SSL through multiphoton polymerization printing, where connected microscale sliders form a basic unit that can theoretically be scaled to any size and shape for SSL applications. Our approach facilitates the development of SSL-based devices and the realization of macroscale SSL. Additionally, it may inspire novel sliding-based transfer methods for two-dimensional materials by leveraging their inherent sliding characteristics.

Keywords:  assembly; graphite sliders; macroscale; massive transfer; structural superlubricity

DOI:  https://doi.org/10.1021/acsami.5c02336
Soft Matter. 2025 Apr 08.

A cofactor mediated supramolecular oligo-adenine triplex for reprogrammable macroscopic hydrogel assembly.

Alycia Zi Ting Lim, Michael Shao Min Ho, Yujie Ke, Wei Wei Loh, Zhaogang Dong, Fuke Wang, Jason Y C Lim, Xin Ting Zheng, Le Yang, Yuwei Hu.

Noncanonical DNA structures mediated by low-molecular-weight cofactors significantly enrich the arsenal of the DNA toolbox and expand its functional applications. In this study, cyanuric acid (CA), a cofactor with three thymine-like edges, is employed to assemble adenine-rich strands (A-strands) into a parallel noncanonical A-CA triplex configuration through Watson-Crick and Hoogsteen interactions. This assembly occurs at a system pH value below the pKa of the CA cofactor (6.9), where CA is protonated, while its deprotonation at higher pH levels leads to the dissociation of the A-CA triplex into single A-strands and free CA cofactors. The structural transition is fully pH reversible. The A-CA triplex is further utilized as a crosslinking element for reprogrammable macroscopic object assembly, exemplified by hydrogel cubes (5 × 5 × 5 mm), a topic that has been less explored compared to nano- and microscopic constructs. Controlled, modular assembly and disassembly of various configurations, such as square, line, and T-shape, are demonstrated through reversible pH adjustments. This strategy offers a streamlined approach using a single DNA sequence and cofactor for hydrogel modification and complex construction, providing cost-effective, recyclable, and stimuli-responsive functionality, which inspires the development of versatile and adaptive supramolecular systems in chemistry and materials science.

DOI: https://doi.org/10.1039/d5sm00124b
Small Sci. 2024 Nov;4(11): 2400290

Engineering Conductive Hydrogels with Tissue-like Properties: A 3D Bioprinting and Enzymatic Polymerization Approach.

Changbai Li, Sajjad Naeimipour, Fatemeh Rasti Boroojeni, Tobias Abrahamsson, Xenofon Strakosas, Yangpeiqi Yi, Rebecka Rilemark, Caroline Lindholm, Venkata K Perla, Chiara Musumeci, Yuyang Li, Hanne Biesmans, Marios Savvakis, Eva Olsson, Klas Tybrandt, Mary J Donahue, Jennifer Y Gerasimov, Robert Selegård, Magnus Berggren, Daniel Aili, Daniel T Simon.

  Hydrogels are promising materials for medical devices interfacing with neural tissues due to their similar mechanical properties. Traditional hydrogel-based bio-interfaces lack sufficient electrical conductivity, relying on low ionic conductivity, which limits signal transduction distance. Conducting polymer hydrogels offer enhanced ionic and electronic conductivities and biocompatibility but often face challenges in processability and require aggressive polymerization methods. Herein, we demonstrate in situ enzymatic polymerization of π-conjugated monomers in a hyaluronan (HA)-based hydrogel bioink to create cell-compatible, electrically conductive hydrogel structures. These structures were fabricated using 3D bioprinting of HA-based bioinks loaded with conjugated monomers, followed by enzymatic polymerization via horseradish peroxidase. This process increased the hydrogels' stiffness from about 0.6 to 1.5 kPa and modified their electroactivity. The components and polymerization process were well-tolerated by human primary dermal fibroblasts and PC12 cells. This work presents a novel method to fabricate cytocompatible and conductive hydrogels suitable for bioprinting. These hybrid materials combine tissue-like mechanical properties with mixed ionic and electronic conductivity, providing new ways to use electricity to influence cell behavior in a native-like microenvironment.

Keywords:  3D printing; cell scaffold; conducting polymer; in vitro; polymerization

DOI:  https://doi.org/10.1002/smsc.202400290
Proc Natl Acad Sci U S A. 2025 Apr 15. 122(15): e2403083122

Chemically active wetting.

Susanne Liese, Xueping Zhao, Christoph A Weber, Frank Jülicher.

  Wetting of liquid droplets on passive surfaces is ubiquitous in our daily lives, and the governing physical laws are well understood. When surfaces become active, however, the governing laws of wetting remain elusive. Here, we propose chemically active wetting as a class of active systems where the surface is active due to a binding process that is maintained away from equilibrium. We derive the corresponding nonequilibrium thermodynamic theory and show that active binding fundamentally changes the wetting behavior, leading to steady, nonequilibrium states with droplet shapes reminiscent of a pancake or a mushroom. The origin of such anomalous shapes can be explained by mapping to electrostatics, where pairs of binding sinks and sources correspond to electrostatic dipoles along the triple line. This is an example of a more general analogy, where localized chemical activity gives rise to a multipole field of the chemical potential. The underlying physics is relevant for cells, where droplet-forming proteins can bind to membranes accompanied by the turnover of biological fuels.

Keywords:  nonequilibrium thermodynamics; phase separation; wetting

DOI:  https://doi.org/10.1073/pnas.2403083122
Environ Sci Process Impacts. 2025 Apr 10.

Designing for degradation: the importance of considering biotic and abiotic polymer degradation.

Omar Tantawi, Wontae Joo, Elijah E Martin, Sarah H M Av-Ron, K'yal R Bannister, Kristala L J Prather, Bradley D Olsen, Desiree L Plata.

Considering the increasing global plastic demand, there is a critical need to gain insight into environmental processes that govern plastic degradation in order to inform novel design of sustainable polymers. Current biological degradation testing standards focus on formation of CO2 (i.e., mineralization) alone as a diagnostic, ultimately limiting identification of structure-degradation relationships in a timely fashion. This work developed a sequential abiotic (i.e., photodegradation and hydrolysis) and biotic degradation test and applied it to a suite of 18 polymers, including ten lab produced, novel polyhydroxyalkanoate polyesters, and eight commercially available, bio-based (i.e., polylactic acid and poly-3-hydroxybutyrate) and fossil-derived (i.e., polystyrene, polypropylene, low density polyethylene, poly(ethylene terephthalate) and tire rubber) polymers. Biomineralization alone following standard methods (i.e., ASTM 6691-17, ISO 23977-1 2020) underestimated polymer degradation up to two-fold over 28 days. Simulated sunlight enhanced the overall polymer degradation by mobilizing dissolved organic carbon (DOC). After photoirradiation, up to 100% of released dissolved organic carbon was bioavailable for marine microbes over 14 days. Photodegradation and hydrolysis could be explained by structural drivers in the commodity polymers, and the lab-synthesized polymers illustrated a limit to total degradation beyond which no enhancements in degradation were achieved. Taken together, this workflow allows for relatively fast experimental determination of environmentally relevant stimuli to help support eventual elucidation of structure-property relationships for enhanced a priori design of degradable polymers.

DOI: https://doi.org/10.1039/d5em00079c
Nat Commun. 2025 Apr 12. 16(1): 3482

Mutualism breakdown underpins evolutionary rescue in an obligate cross-feeding bacterial consortium.

Ignacio J Melero-Jiménez, Yael Sorokin, Ami Merlin, Jiawei Li, Alejandro Couce, Jonathan Friedman.

Populations facing lethal environmental change can escape extinction through rapid genetic adaptation, a process known as evolutionary rescue. Despite extensive study, evolutionary rescue is largely unexplored in mutualistic communities, where it is likely constrained by the less adaptable partner. Here, we explored empirically the likelihood, population dynamics, and genetic mechanisms underpinning evolutionary rescue in an obligate mutualism involving cross-feeding of amino acids between auxotrophic Escherichia coli strains. We found that over 80% of populations overcame a severe decline when exposed to two distinct types of abrupt, lethal stress. Of note, in all cases only one of the strains survived by metabolically bypassing the auxotrophy. Crucially, the mutualistic consortium exhibited greater sensitivity to both stressors than a prototrophic control strain, such that reversion to autonomy was sufficient to alleviate stress below lethal levels. This sensitivity was common across other stresses, suggesting it may be a general feature of amino acid-dependent obligate mutualisms. Our results reveal that evolutionary rescue may depend critically on the specific genetic and physiological details of the interacting partners, adding rich layers of complexity to the endeavor of predicting the fate of microbial communities facing intense environmental deterioration.

DOI: https://doi.org/10.1038/s41467-025-58742-1
Nature. 2025 Apr 09.

Reprogramming site-specific retrotransposon activity to new DNA sites.

Christopher W Fell, Lukas Villiger, Justin Lim, Masahiro Hiraizumi, Dario Tagliaferri, Matthew T N Yarnall, Anderson Lee, Kaiyi Jiang, Alisan Kayabolen, Rohan N Krajeski, Cian Schmitt-Ulms, Harsh Ramani, Sarah M Yousef, Nathaniel Roberts, Christopher A Vakulskas, Hiroshi Nishimasu, Omar O Abudayyeh, Jonathan S Gootenberg.

Retroelements have a critical role in shaping eukaryotic genomes. For instance, site-specific non-long terminal repeat retrotransposons have spread widely through preferential integration into repetitive genomic sequences, such as microsatellite regions and ribosomal DNA genes1-6. Despite the widespread occurrence of these systems, their targeting constraints remain unclear. Here we use a computational pipeline to discover multiple new site-specific retrotransposon families, profile members both biochemically and in mammalian cells, find previously undescribed insertion preferences and chart potential evolutionary paths for retrotransposon retargeting. We identify R2Tg, an R2 retrotransposon from the zebra finch, Taeniopygia guttata, as an orthologue that can be retargeted by payload engineering for target cleavage, reverse transcription and scarless insertion of heterologous payloads at new genomic sites. We enhance this activity by fusing R2Tg to CRISPR-Cas9 nickases for efficient insertion at new genomic sites. Through further screening of R2 orthologues, we select an orthologue, R2Tocc, with natural reprogrammability and minimal insertion at its natural 28S site, to engineer SpCas9H840A-R2Tocc, a system we name site-specific target-primed insertion through targeted CRISPR homing of retroelements (STITCHR). STITCHR enables the scarless, efficient installation of edits, ranging from a single base to 12.7 kilobases, gene replacement and use of in vitro transcribed or synthetic RNA templates. Inspired by the prevalence of nLTR retrotransposons across eukaryotic genomes, we anticipate that STITCHR will serve as a platform for scarless programmable integration in dividing and non-dividing cells, with both research and therapeutic applications.

DOI: https://doi.org/10.1038/s41586-025-08877-4
Small. 2025 Apr 07. e2412538

Cellulose Gels: Functional Design and Promising Smart Applications.

Geyuan Jiang, Guangwen Xu, Qinqin Xia, Haipeng Yu, Dawei Zhao.

  Cellulose, the most abundant natural polymer, is characterized by its unique molecular architecture, which enables its strategic engineering into functional gel materials such as ionogels and hydrogels. Despite significant advancements in cellulose gel technology, especially in the area of ionogels, challenges remain in fully exploring their functional properties and broadening their applications. This review examines the development and evolution of cellulose gels, focusing on new directions in molecular-scale design for these functional materials. Strategies to enhance the mechanical performance, ionic conductivity, and self-healing properties of cellulose gels are systematically outlined, emphasizing the regulation of molecular assembly, the creation of dynamic bonds, and the design of switchable supramolecular networks. Furthermore, the emerging applications of these cellulose gels in electronic skins, flexible electronics, smart devices, and biomedical science are discussed. Performance development targets and trends for cellulose gels are identified, highlighting the potential of molecular-scale design and the role of artificial intelligence in predicting and accelerating the design process. This work proposes feasible and scalable design strategies aimed at improving the functional properties and broadening the applications of cellulose gels.

Keywords:  cellulose gels; ionic conductivity; mechanical properties; molecular design; smart devices

DOI:  https://doi.org/10.1002/smll.202412538
Cell. 2025 Apr 04. pii: S0092-8674(25)00289-2. [Epub ahead of print]

Extracellular respiration is a latent energy metabolism in Escherichia coli.

Biki Bapi Kundu, Jayanth Krishnan, Richard Szubin, Arjun Patel, Bernhard O Palsson, Daniel C Zielinski, Caroline M Ajo-Franklin.

  Diverse microbes utilize redox shuttles to exchange electrons with their environment through mediated extracellular electron transfer (EET), supporting anaerobic survival. Although mediated EET has been leveraged for bioelectrocatalysis for decades, fundamental questions remain about how these redox shuttles are reduced within cells and their role in cellular bioenergetics. Here, we integrate genome editing, electrochemistry, and systems biology to investigate the mechanism and bioenergetics of mediated EET in Escherichia coli, elusive for over two decades. In the absence of alternative electron sinks, the redox cycling of 2-hydroxy-1,4-naphthoquinone (HNQ) via the cytoplasmic nitroreductases NfsB and NfsA enables E. coli respiration on an extracellular electrode. E. coli also exhibits rapid genetic adaptation in the outer membrane porin OmpC, enhancing HNQ-mediated EET levels coupled to growth. This work demonstrates that E. coli can grow independently of classic electron transport chains and fermentation, unveiling a potentially widespread new type of anaerobic energy metabolism.

Keywords:  adaptive laboratory evolution; anaerobic metabolism; electron shuttles; extracellular electron transfer; flux balance analysis; iModulon analysis; nitroreductases; redox homeostasis

DOI:  https://doi.org/10.1016/j.cell.2025.03.016