bims-enlima Biomed News
on Engineered living materials
Issue of 2025–06–22
38 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool



  1. Acta Biomater. 2025 Jun 12. pii: S1742-7061(25)00413-1. [Epub ahead of print]
      The development of perfusable and multiscale vascular networks remains one of the largest challenges in tissue engineering. As such, there is a need for the creation of customizable and facile methods to produce robustly vascularized constructs. In this study, secondarily crosslinkable (clickable) poly(ethylene glycol)-norbornene (PEGNB) microbeads were produced and evaluated for their ability to sequentially support suspension bioprinting and microvascular self-assembly towards the aim of engineering hierarchical vasculature. The clickable PEGNB microbead slurry exhibited mechanical behavior suitable for suspension bioprinting of sacrificial bioinks, could be UV crosslinked into a granular construct post-print, and withstood evacuation of the bioink and subsequent perfusion of the patterned void space. Endothelial and stromal cells co-embedded within jammed RGD-modified PEGNB microbead slurries assembled into capillary-scale vasculature after secondary crosslinking of the beads into granular constructs, with endothelial tubules forming within the interstitial space between microbeads and supported by the perivascular association of the stromal cells. Microvascular self-assembly was not impacted by printing sacrificial bioinks into the cell-laden microbead support bath before UV crosslinking. Collectively, these results demonstrate that clickable PEGNB microbeads are a versatile substrate for both suspension printing and microvascular culture and may be the foundation for a promising methodology to engineer hierarchical vasculature. STATEMENT OF SIGNIFICANCE: In this study, we leveraged and combined advances in microgel biomaterials, granular hydrogels, suspension bioprinting, and vascular biology to create relatively large volume (>500 mm3) vascularized constructs. We fabricated secondarily crosslinkable (clickable) poly(ethylene glycol)-norbornene (PEGNB) microbeads and demonstrated their ability to sequentially support suspension bioprinting and microvascular self-assembly towards the aim of engineering hierarchical vasculature. To the best of our knowledge, this is the first study that uses PEG microgels as supportive materials for bioprinting, and one of the first papers to document microvascular self-assembly within granular constructs. The combination of top-down and bottom-up approaches within a single construct represents a significant and innovative contribution that we believe will be of broad interest to the biomaterials and regenerative medicine communities.
    Keywords:  MAP gels; Microgels; Poly(ethylene glycol); Suspension bioprinting; Vascularization
    DOI:  https://doi.org/10.1016/j.actbio.2025.06.006
  2. Commun Biol. 2025 Jun 17. 8(1): 933
      Plasmids and the model bacterium Escherichia coli are at the heart of recombinant gene technologies. Plasmids are handled in test tubes with enzymes such as restriction endonucleases, ligases, and polymerases. However, with the increasing demand for larger and more complex designs, in vitro manipulation constitutes a bottleneck. By combining recombination with genetic selection, in vivo manipulation of genomic DNA is becoming routine but is yet to be developed as a versatile and reliable way to make plasmid DNA. Here, we present a robust methodology for plasmid recombineering in E. coli using a triple-selection system customized for efficient performance at any copy number. Equipped with this genetic selection cassette, we generate a toolbox of plasmids in a standardized framework with popular genetic modules. By reducing the time and resources for making recombinant DNA, this approach should enable automation and accelerate the development of biological solutions.
    DOI:  https://doi.org/10.1038/s42003-025-08361-9
  3. ACS Synth Biol. 2025 Jun 17.
      With advancements in synthetic biology and metabolic engineering, microorganisms can now be engineered to perform increasingly complex functions, which may be limited by the resources available in individual cells. Introducing heterologous metabolic pathways introduces both genetic burden due to the competition for cellular transcription and translational machinery, as well as metabolic burden due to the redirection of metabolic flux from the native metabolic pathways. Division of labor in synthetic microbial communities offers a promising approach to enhance metabolic efficiency and resilience in bioproduction. By distributing complex metabolic pathways across multiple subpopulations, the resource competition and metabolic burden imposed on an individual cell are reduced, potentially enabling more efficient production of target compounds. Violacein is a high-value pigment with antitumor properties that exemplifies such a challenge due to its complex bioproduction pathway, imposing a significant metabolic burden on host cells. In this study, we investigated the benefits of division of labor for violacein production by splitting the violacein bioproduction pathway between two subpopulations of Escherichia coli-based synthetic communities. We tested several pathway splitting strategies and reported that splitting the pathway into two subpopulations expressing VioABE and VioDC at a final composition of 60:40 yields a 2.5-fold increase in violacein production as compared to a monoculture. We demonstrated that the coculture outperforms the monoculture when both subpopulations exhibit similar metabolic burden levels, resulting in comparable growth rates, and when both subpopulations are present in sufficiently high proportions.
    Keywords:  division of labor; metabolic engineering; precision fermentation; synthetic biology; synthetic microbial communities; violacein biosynthesis
    DOI:  https://doi.org/10.1021/acssynbio.5c00120
  4. ACS Appl Polym Mater. 2025 Jun 13. 7(11): 7566-7574
      Additive manufacturing of elastomers enables the fabrication of many technologically important structures and devices. However, it remains a challenge to develop soft and stretchable elastomers for vat photopolymerization (VP) printing, one of the most used additive manufacturing techniques for producing objects with relatively high resolution and smooth finishes. Here, we report a modular soft stretchable low-cost elastomer resin for VP printing. The resin consists of mainly commodity acrylates and can be photocured to form a dual-network containing covalent crosslinks and reversible double hydrogen bonds. Controlling the ratio of covalent and reversible crosslinks enables elastomers with an exceptional combination of softness and stretchability (Young's modulus of 20-150 kPa and tensile breaking strain of 510-1350%) that cannot be achieved by existing VP resins. Using a customized VP printing platform, we transform this resin into complex three-dimensional (3D) structures. We develop an instrument to show that the 3D structures possess extreme dissipative properties, such that they can protect brain-like soft gels from impact damage in reducing the severity of impact by 75%. Together with the low cost of raw chemicals and modular nature of the design, these soft stretchable elastomer resins provide a class of feedstock for high-fidelity additive manufacturing of functional structures.
    Keywords:  dissipative structures; low-cost; modular synthesis; soft stretchable elastomers; vat photopolymerization printing
    DOI:  https://doi.org/10.1021/acsapm.5c01217
  5. Phys Rev E. 2025 May;111(5-1): 054412
      The programming of computations in living cells is achieved by manipulating information flows within genetic networks. Typically, gene expression is discretized into high and low levels, representing 0 and 1 logic values to encode a single bit of information. However, molecular signaling and computation in living systems operate dynamically, stochastically, and continuously, challenging this binary paradigm. While stochastic and probabilistic models of computation address these complexities, there is a lack of work unifying these concepts to implement computations tailored to these features of living matter. Here we design genetic networks for stochastic and probabilistic computing, developing the underlying theory. Moving beyond the digital framework, we propose random pulses and probabilistic-bits (p-bits) as better candidates for encoding and processing information genetic networks. Encoding information through the frequency of expression burst frequency offers robustness to noise, while p-bits enable unique circuit designs with features like invertibility. We illustrate these advantages by designing circuits and providing mathematical models and simulations to demonstrate their functionality. Our approach to stochastic and probabilistic computing not only advances our understanding of information processing in biological systems but also opens new possibilities for designing genetic circuits with enhanced capabilities.
    DOI:  https://doi.org/10.1103/PhysRevE.111.054412
  6. ACS Synth Biol. 2025 Jun 17.
      Deciphering gene function to understand the genetic basis of microbial phenotypes in a high-throughput manner is crucial for bacterial engineering. However, efficient tools for generating genome-wide gene activation mutant libraries to enable gain-of-function analyses remain limited. Here, we developed a Tn5 transposase-based system for efficient genome-wide gene activation in Escherichia coli. The cargo DNA incorporated a tetracycline-inducible promoter Ptet and a kanamycin resistance gene, enabling selective growth and conditional gene activation. The system achieved near-random integration with an insertion frequency of approximately 2.83 × 107 cfu/μg DNA. Both in vitro and in vivo transposition results demonstrated the effective activation of specific and nonspecific genes. Using this system, we identified three putative transporters that, despite being unrelated to glycine export, significantly enhanced glycine resistance in E. coli. These results highlight the utility of this method for genotype-phenotype mapping and strain optimization, offering a powerful tool for synthetic biology and functional genomics.
    Keywords:  Tn5 transposase; gene activation; genome-wide screening; glycine resistance; transposition
    DOI:  https://doi.org/10.1021/acssynbio.5c00170
  7. Nat Methods. 2025 Jun 16.
      Biomolecular condensates organize numerous subcellular processes and have been implicated in diseases, including neurodegeneration and cancer. Protein sequences intrinsically encode their propensity to form condensates, but specific sequence features that regulate this behavior have not been systematically explored at scale. Here, we develop CondenSeq, a high-throughput pooled imaging with in situ sequencing approach to measure propensities of thousands of protein sequences to form nuclear condensates. Leveraging the large scale of these experiments, we evaluated the impacts of dozens of sequence features across a wide range of sequence contexts, identifying several features with highly consistent, context-independent effects and others with less-consistent effects. We also identified multiple classes of condensates and discovered distinct sequence properties that drive their formation. Our results provide a systematic overview of the relationships between protein sequences and nuclear condensate formation and establish a general approach for further dissecting these relationships at scale.
    DOI:  https://doi.org/10.1038/s41592-025-02726-y
  8. Cell. 2025 Jun 11. pii: S0092-8674(25)00572-0. [Epub ahead of print]
      Metazoan life requires the coordinated activities of thousands of genes in spatially organized cell types. Understanding the basis of tissue function requires approaches to dissect the genetic control of diverse cellular and tissue phenotypes in vivo. Here, we present Perturb-Multimodal (Perturb-Multi), a paired imaging and sequencing method to construct large-scale, multimodal genotype-phenotype maps in tissues with pooled genetic perturbations. Using imaging, we identify perturbations in individual cells while simultaneously measuring their gene expression profiles and subcellular morphology. Using single-cell sequencing, we measure full transcriptomic responses to the same perturbations. We apply Perturb-Multi to study hundreds of genetic perturbations in the mouse liver. Our data suggest the genetic regulators and mechanisms underlying the dynamic control of hepatocyte zonation, the unfolded protein response, and steatosis. Perturb-Multi accelerates discoveries of the genetic basis of complex cell and tissue physiology and provides critical training data for emerging machine learning models of cellular function.
    Keywords:  RCA-MERFISH; hepatocyte stress response; in vivo pooled screening; lipid droplet accumulation; liver zonation; machine learning morphology; multimodal phenotyping; multiplexed RNA imaging; multiplexed protein imaging; scRNA-seq
    DOI:  https://doi.org/10.1016/j.cell.2025.05.022
  9. Nano Lett. 2025 Jun 16.
      Dip-pen nanolithography (DPN) represents a versatile approach for depositing nanoscale quantities of fluids onto surfaces. Here, we show that overwriting─or patterning fluids onto previously deposited features─results in patterns with predictable size and composition that are useful for combinatorial materials experiments. We combine fluorescence microscopy and inertial sensing to show that multiple fluid reservoirs can be mixed together to realize combinatorial libraries of nanoscale features with known mass and composition. As an example of the utility of this approach from a materials discovery perspective, we employ this process to study the mechanics and swelling behavior of polyethylene glycol hydrogels with different compositions. Given that this approach allows one to prepare compositional gradients using less than a microgram of material and functionality to evaluate these using the versatility of the atomic force microscope, it has tremendous potential for the discovery and optimization of performance materials for catalysis, mechanics, photonics, and electronics.
    Keywords:  combinatorial library; dip-pen nanolithography; nanopatterning; polymers; scanning probe lithography
    DOI:  https://doi.org/10.1021/acs.nanolett.5c02539
  10. ACS Synth Biol. 2025 Jun 20. 14(6): 1873-1878
      Both Japan and the UK have recognized the growing importance of synthetic and engineering biology for transforming life science research and transitioning toward a sustainable biobased economy. Such a shift will require extensive international cooperation and collaboration. In this viewpoint, we provide a summary of the recent "Japan-UK Synthetic Biology Conference, Spring 2025" that aimed to facilitate new links between researchers across the broad field of synthetic biology. We cover the core scientific topics discussed, distill some of the emerging trends, and outline the remaining challenges that are hampering progress. We end by highlighting some of the ways in which international collaborations may help address these issues through a combination of sharing expertise, national infrastructures, and aligned funding.
    Keywords:  Japan; UK; engineering biology; international collaboration; synthetic biology
    DOI:  https://doi.org/10.1021/acssynbio.5c00232
  11. Biomacromolecules. 2025 Jun 20.
      The hydrogel "affinity trap" engineered here from peptides and nucleic acids into dynamic supramolecular structures offered the opportunity to measure physiological concentrations of tissue-specific microRNA expression and degradation, which are symptomatic for diseased cells and tissues. Hydrogel size-discriminating properties allowed to segregate microRNAs from complex biological media into a hydrogel matrix and entrap the target sequence via hybridization with a hydrogel-immobilized "capture" probe, where it could be detected through fluorescence quenching. We demonstrated the size-selective permeability of the hydrogel that provided a protective microenvironment for microRNAs and detection probes from cellular biological interference and afforded selective self-assembly and detection of oncogenic microRNA-21 (miR-21) in the presence of cell extracts, which is otherwise detrimental for detection in a gel-free solution. We were also able to monitor the degradation of unlabeled miR-21 by natural (RNase A and H) and synthetic (miR-21-RNase) ribonucleases and their synergistic actions, which could be potentially useful in the therapeutic knockdown of pathogenic RNAs.
    DOI:  https://doi.org/10.1021/acs.biomac.5c00594
  12. Commun Mater. 2025 ;6(1): 121
      Electrically conductive hydrogels can simulate the sensory capabilities of natural skin, such that they are well-suited for electronic skin. Unfortunately, currently available electronic skin cannot detect multiple stimuli in a selective manner. Inspired by the deep eutectic solvent chemistry of the frog Lithobates Sylvaticus, we introduce a double network granular organogel capable of simultaneously detecting mechanical deformation, structural damage, changes in ambient temperature, and humidity. The deep eutectic solvent chemistry adds an additional benefit: Thanks to strong hydrogen bonding, our sensor can recover 97% of the Young's modulus after being damaged. The sensing performance and self-healing capacity are maintained within a temperature range of -20 °C to 50 °C for at least 2 weeks. We exploit the granular nature of this system to direct ink to write a cm-sized frog and e-skin wearables. We realize selective tactile perception by training recurrent neural networks to achieve sensory stimulus classification between the temperature and strain with 98% accuracy.
    Keywords:  Biomedical engineering; Chemical engineering; Materials science
    DOI:  https://doi.org/10.1038/s43246-025-00839-7
  13. Sci Adv. 2025 Jun 20. 11(25): eadr6399
      The ecological and evolutionary success of multicellular lineages stems substantially from their increased size relative to unicellular ancestors. However, large size poses biophysical challenges, especially regarding nutrient transport: These constraints are typically overcome through multicellular innovations. Here, we show that an emergent biophysical mechanism-spontaneous fluid flows arising from metabolically generated density gradients-can alleviate constraints on nutrient transport, enabling exponential growth in nascent multicellular clusters of yeast lacking any multicellular adaptations for nutrient transport or fluid flow. Beyond a threshold size, the metabolic activity of experimentally evolved snowflake yeast clusters drives large-scale fluid flows that transport nutrients throughout the cluster at speeds comparable to those generated by ciliary actuation in extant multicellular organisms. These flows support exponential growth at macroscopic sizes that theory predicts should be diffusion limited. This demonstrates how simple physical mechanisms can act as a "biophysical scaffold" to support the evolution of multicellularity by opening up phenotypic possibilities before genetically encoded innovations.
    DOI:  https://doi.org/10.1126/sciadv.adr6399
  14. Mater Horiz. 2025 Jun 19.
      Hydrogels are three-dimensional, crosslinked networks of hydrophilic polymers with mesh sizes ranging from nanometers to microns. Different from solvent-free networks such as elastomers, hydrogels can retain significant amounts of water within their structure, enabling the diffusion of small molecules (e.g., ions, solvents, monomers) throughout the network. These small molecules often play a pivotal role in altering the hydrogel structure by driving processes such as ionic crosslinking, phase separation, and crystallization. Extensive studies have demonstrated that small molecules can influence hydrogel networks either through direct interactions or by inducing changes in the surrounding environment, both of which can lead to substantial enhancement in mechanical performance; yet this area has not been comprehensively reviewed. To address this gap, this paper summarizes how small molecule-induced structural transformations contribute to hydrogel toughening and outlines design strategies that employ these effects. The review also highlights cutting-edge applications and discusses challenges and opportunities in developing tough hydrogels with the aid of small molecules. We hope this review provides helpful insights into the impact of small molecules on macromolecular networks and fosters the development of next-generation soft materials.
    DOI:  https://doi.org/10.1039/d5mh00588d
  15. Methods Mol Biol. 2025 ;2931 241-248
      Synthetic poly(amino acid)s are a class of promising materials for biomedical applications. Ring opening polymerization (ROP) based on N-carboxyanhydrides (NCAs) is a commonly used method for synthesizing poly(amino acid)s with controlled molecular weight distribution and tunable amino acid sequence. Herein, we introduce two representative protocols for synthesizing poly(amino acid)s with homogenous or multiblock amino acid units based on ROP.
    Keywords:  Block copolymers; N-carboxyanhydride; Peptides; Poly(amino acid)s; Ring opening polymerization
    DOI:  https://doi.org/10.1007/978-1-0716-4562-8_18
  16. Nat Chem Biol. 2025 Jun 13.
      Chemically induced proximity (CIP) has remarkably advanced the development of molecular and cellular therapeutics. To maximize therapeutic potential, there is a pressing need to expand the repertoire of CIP systems of translational values, favoring chemical ligands that are cost-effective, structurally simple, biocompatible, reversible and have minimal side effects. Here, we present a salicylic acid (SA)-mediated binary association system (SAMBA), evolved from a tobacco SA receptor, that enables rapid protein-protein heterodimerization in response to SA or aspirin after hydrolysis. We demonstrate the broad applicability of SAMBA in various biological contexts, including SA-dependent reprogramming of a protein-based reaction-diffusion system, graded gating of calcium channels, inducible initiation of receptor tyrosine kinase-mediated signaling and gene expression, and tunable activation of chimeric antigen receptor T cells. Our work establishes SAMBA as a versatile chemogenetic platform that allows temporal control of biological processes and therapeutic cells both in vitro and in vivo.
    DOI:  https://doi.org/10.1038/s41589-025-01918-z
  17. Nature. 2025 Jun 17.
      
    Keywords:  Biochemistry; Biophysics; Cell biology; Drug discovery; Technology
    DOI:  https://doi.org/10.1038/d41586-025-01840-3
  18. Nanoscale. 2025 Jun 20.
      The arene-perfluoroarene (AP) interaction, arising between polyaromatic hydrocarbons and their perfluorinated counterparts, features an inverted electron distribution induced by fluorination compared to hydrocarbons. This interaction exhibits enhanced binding affinity compared to conventional π-π interaction and has emerged as a powerful tool for directing self-assembly processes to fabricate functional materials. This review outlines two construction strategies for AP systems: (1) covalent integration of electron-rich (arene) and electron-deficient (perfluoroarene) moieties within a single building block and (2) assembly of discrete complementary components separately functionalized with arene and perfluoroarene units. The structural diversity of supramolecular architectures driven by the AP interaction is analyzed, emphasizing their programmable geometries and electronic properties. Furthermore, we systematically summarize the applications of AP interaction directed assemblies in photoelectric devices and circularly polarized luminescent (CPL) materials, where tailored intermolecular AP interactions optimize the optoelectronic performance. We also highlight their application in synthetic chemistry and recognition. This review underscores the versatility of AP interactions as a design principle for advanced functional materials, bridging supramolecular chemistry with interdisciplinary applications in materials science, catalysis, and biomedicine.
    DOI:  https://doi.org/10.1039/d5nr01626f
  19. Commun Biol. 2025 Jun 19. 8(1): 940
      Translating ribosomes must wait after each elongation step for a new ternary complex (EF-Tu ⋅ aa-tRNA ⋅ GTP) to arrive, facilitating rapid codon recognition testing. We recently showed that this wait-time rate-limits elongation in Escherichia coli due to competitive combinatoric searching through crowded cytoplasm by thousands of E. coli's 42 unique ternary complexes. Here, we investigate whether ribosomal L12 subunits pool translation molecules to reduce this wait time. We mimic transport and reactions underlying elongation in a physiologically accurate, physically-resolved model of crowded cytoplasm. We find that L12 pre-loading as much as doubles translation rate by reducing diffusive search time. But more L12 is not always better: faster-growing bacteria tend to have fewer L12. We resolve this apparent contradiction by demonstrating tradeoffs between binding and novel sampling as a function of copy number in E. coli. Variable L12 copy numbers may thus have evolved for fast or slow bacterial growth as complementary survival strategies.
    DOI:  https://doi.org/10.1038/s42003-025-08366-4
  20. Nat Chem Biol. 2025 Jun 19.
      Click chemistry is a powerful concept that refers to a set of covalent bond-forming reactions with highly favorable properties. In this Perspective, I outline the analogous concept of click biology as a set of reactions derived from the regular building blocks of living cells, rapidly forming covalent bonds to specific partners under cell-friendly conditions. Click biology using protein components employs canonical amino acids and may react close to the diffusion limit, with selectivity in living cells amid thousands of components generated from the same building blocks. I discuss how the criteria for click chemistry can be applied or modified to fit the extra constraints of click biology and achieve favorable characteristics for biological research. Existing reactions that may be described as click biology include split intein reconstitution, spontaneous isopeptide bond formation by SpyTag and SpyCatcher and suicide enzyme reaction with small-molecule ligands (HaloTag and SNAP-tag). I also describe how click biology has created new possibilities in fields including molecular imaging, mechanobiology, vaccines and engineering cellular intelligence.
    DOI:  https://doi.org/10.1038/s41589-025-01944-x
  21. Ann Biomed Eng. 2025 Jun 17.
      The extracellular matrix (ECM) is a three-dimensional network of polysaccharides and proteins that provides biochemical signals and structural rigidity to cells. In addition to structural support, the ECM provides dynamic mechanical properties such as viscoelasticity. Scientifically, viscoelasticity is the time-dependent response of materials under stress. Due to the viscoelastic behavior of the ECM, viscoelasticity plays a critical role in regulating and stimulating cellular behaviors such as adhesion, proliferation, differentiation, and migration, as well as tissue morphogenesis and remodeling. Scientific knowledge about viscoelasticity usually originates from materials science where physical parameters are well defined. Hence, understanding materials' physical/mechanical behaviors (especially biomaterials in biological contexts) and mathematical modeling related to viscoelasticity are important to achieve useful results. On the other hand, recent advances in the development of biophysical instruments for measuring viscoelasticity have revealed a strong link between material properties and physiological systems and have emerged as important diagnostic tools for investigating the viscoelastic behavior of cells and tissues. Therefore, this review, focusing on matrix viscoelasticity, explains the viscoelastic nature of cells/tissues, examines the impact of matrix viscoelasticity on cellular processes, reviews the role of engineered biomaterials in improving cellular behaviors, and finally discusses modern experimental techniques for measuring viscoelasticity at the cellular level.
    Keywords:  Cellular behavior; Extracellular matrix; Mechanobiology; Tissue regeneration; Viscoelasticity
    DOI:  https://doi.org/10.1007/s10439-025-03767-2
  22. ACS Appl Mater Interfaces. 2025 Jun 16.
      The integration of 3D printing into the manufacture of recycled structural color components presents a compelling alternative to conventional dyes and pigments. This paper proposes a processing strategy combining colloidal nanosphere self-assembly, twin-screw extrusion, and FDM 3D printing to rapidly produce noniridescent structural color components. The twin-screw extrusion mixes nanospheres with resin by using thermal shear forces to arrange nanospheres uniformly, creating structural color filaments (SCFs) for 3D printing. Using FDM 3D printing, various structural color patterns and three-dimensional structural color models (SCMs) are successfully fabricated. The results demonstrate that colloidal nanospheres can achieve regular arrangement within seconds under thermal shear, with the extruded filaments and printed models exhibiting pronounced noniridescent structural colors on a black substrate. Furthermore, SCFs and 3D-printed SCMs demonstrate excellent mechanical properties, with tensile strengths reaching 20.1 and 11.5 MPa, respectively. Moreover, this technology also features advantages such as material recyclability, low cost, low energy consumption, and flexibility in customization flexibility. These findings provide valuable insights into the integration of photonic crystals with 3D printing, underscoring the extensive application potential of noniridescent structural color materials in the production of complex patterns and functional components.
    Keywords:  3D printing; nanospheres; noniridescent structural colors; structural color filaments; structural color models; twin-screw extrusion
    DOI:  https://doi.org/10.1021/acsami.5c06491
  23. Nature. 2025 Jun 18.
      
    Keywords:  Chemistry; Sustainability
    DOI:  https://doi.org/10.1038/d41586-025-01876-5
  24. Nat Chem Biol. 2025 Jun 16.
      Engineered peroxisomes hold promise as a highly versatile platform for compartmentalizing engineered metabolic pathways, insulating them from native cellular factors to prevent undesired crosstalk. However, native peroxisomes often lack the required substrates and cofactors in their lumen; accordingly, nonnative membrane proteins (MPs) must be recruited to the peroxisomal membrane to support heterologous pathways requiring these molecules. We developed a robust, modular 'chauffeur' strategy that enables MP folding in the endoplasmic reticulum (ER) followed by trafficking to the peroxisomal membrane through an engineered interaction in the cytosol with a transmembrane domain natively trafficked from the ER to the peroxisome. We demonstrate the modularity of this strategy by successfully redirecting multiple MP cargoes, including heterologous plant MPs, and observed increased titers for a monoterpene biosynthetic pathway. This strategy overcomes the challenges of misfolding and sorting of MPs to the peroxisome and, accordingly, expands the repertoire of pathways that can be compartmentalized into this organelle.
    DOI:  https://doi.org/10.1038/s41589-025-01948-7
  25. Small. 2025 Jun 20. e2504497
      Interfacial polymerization (IP) is widely used to fabricate high-performance membranes, yet the molecular-level dynamics that govern monomer transport across liquid-liquid interfaces remain poorly understood. Here it is reported that sub-nanoscale "water fingers"-transient chains of water molecules-modulate the interfacial behavior of amine monomers during IP, dictating the structure and performance of the resulting polyamide films. Using molecular dynamics simulations of archetypal membrane-forming systems (m-phenylenediamine (MPD)-trimesoyl chloride (TMC) for reverse osmosis and piperazine (PIP)-TMC for nanofiltration), it is revealed that water fingers differentially stabilize monomer transport across the aqueous-organic interface, correlating with experimentally observed disparities in film density and permeability. These findings offer a new physical picture of interfacial reactivity, establishing water fingers as critical, tunable elements of monomer transport. This work provides mechanistic insights into a century-old reaction and opens new design strategies for ultrathin films and interfacial materials.
    Keywords:  interfacial polymerization; liquid interface; membranes; molecular dynamics; water structures
    DOI:  https://doi.org/10.1002/smll.202504497
  26. Proc Natl Acad Sci U S A. 2025 Jun 24. 122(25): e2309772122
      Circulating monocytes are recruited to the tumor microenvironment, where they can differentiate into macrophages that mediate tumor progression. To reach the tumor microenvironment, monocytes must first extravasate and migrate through the type-1 collagen rich stromal matrix. The viscoelastic stromal matrix around tumors not only stiffens relative to normal stromal matrix, but often exhibits enhanced viscous characteristics, as indicated by a higher loss tangent or faster stress relaxation rate. Here, we studied how changes in matrix stiffness and viscoelasticity impact the three-dimensional (3D) migration of monocytes through stromal-like matrices. Interpenetrating networks of type-1 collagen and alginate, which enable independent tunability of stiffness and stress relaxation over physiologically relevant ranges, were used as confining matrices for 3D culture of monocytes. Increased stiffness and faster stress relaxation independently enhanced the 3D migration of monocytes. Migrating monocytes have an ellipsoidal or rounded wedge-like morphology, reminiscent of amoeboid migration, with accumulation of actin at the trailing edge. Matrix adhesions were dispensable for monocyte migration in 3D, but migration did require actin polymerization and myosin contractility. Mechanistic studies indicate that actin polymerization at the leading edge generates protrusive forces that open a path for the monocytes to migrate through in the confining viscoelastic matrices. Taken together, our findings implicate matrix stiffness and stress relaxation as key mediators of monocyte migration and reveal how monocytes use pushing forces at the leading edge mediated by actin polymerization to generate migration paths in confining viscoelastic matrices.
    Keywords:  3D migration; monocytes; stromal matrix; viscoelasticity
    DOI:  https://doi.org/10.1073/pnas.2309772122
  27. Sci Adv. 2025 Jun 20. 11(25): eadt3352
      In living tissues, collagen networks rarely exist alone because they are embedded within other biological matrices. When combined, collagen networks rigidify via synergistic mechanical interactions and stiffen only with higher mechanical loads. However, how cells respond to the nonlinear elasticity of collagen in hybrid networks remains largely unknown. Here, we demonstrate that when collagen rigidifies by the interpenetration of a second polymer, the amount of force that initially stiffens the network (onset of stiffening, σc) increases and is sufficient to stimulate an increase in intracellular tension. We investigated this effect by precisely controlling the nonlinear elasticity of collagen with the synthetic semiflexible polymer, polyisocyanopeptides. We find that small increases in σc induce a biphasic response in cell-matrix interactions, influencing how cells migrate, proliferate, and generate contractile force. Our results suggest that cells adaptively respond to changes in the nonlinear mechanics of collagen, which may be a mechanistic behavior used during tissue homeostasis or when collagen rigidifies during pathological conditions.
    DOI:  https://doi.org/10.1126/sciadv.adt3352
  28. Small Sci. 2025 Jun;5(6): 2400622
      Protocells offer a versatile material for dissecting cellular processes and developing simplified biomimetic systems by combining biological components with synthetic ones. However, a gap exists between the integrity and complex functionality of native organelles such as nuclei, and bottom-up strategies reducing cellular functions within a synthetic environment. Here, this gap is bridged by incorporating native nuclei into polymeric giant unilamellar vesicles (pGUVs) using double-emulsion microfluidics. It is shown that the nuclei retain their morphology and nuclear envelope integrity, facilitating the import of co-encapsulated peptide-based multicompartment micelles (MCMs) via nuclear localization signals (NLS). Importantly, it is demonstrated that the nuclear import machinery remains functional inside the protocells, and by enriching the GUV interior with nuclear import-promoting factors, the delivery efficiency of NLS-MCMs significantly increases. The findings reveal that nucleated protocells preserve nuclear function and integrity for extended periods, providing a new platform for studying nuclear processes in a simplified, yet biologically relevant, environment. This approach opens avenues for creating advanced biohybrid materials, offering opportunities to investigate organelle behavior and their interactions with cellular components in greater detail. The findings establish a foundation for high-throughput applications in synthetic biology and contribute valuable insights into sustaining complex cellular functions in engineered systems.
    Keywords:  native nuclei; nuclear delivery; peptide multicompartment micelles; polymeric GUVs; protocells
    DOI:  https://doi.org/10.1002/smsc.202400622
  29. Small. 2025 Jun 16. e2504687
      Studies on the dynamics of single cell phenotyping have been hampered by the lack of quantitative high-throughput metabolism assays. Extracellular acidification, a prominent phenotype, yields significant insights into cellular metabolism, including tumorigenicity. Here, it is developed a versatile microfluidic system for single cell optical pH analysis (SCO-pH), which compartmentalizes single cells in 140-pL droplets and immobilizes ≈40,000 droplets in a 2D array for temporal extracellular pH analysis. SCO-pH distinguishes cells undergoing hyperglycolysis induced by oligomycin A from untreated cells by monitoring their extracellular acidification. To facilitate pH sensing in each droplet, a cell-impermeable pH probe is encapsulated and its fluorescence intensities are quantified. Using this approach, hyperglycolytic cells can be differentiated, and single-cell heterogeneity in extracellular acidification dynamics can be concurrently observed. This high-throughput system will be useful in applications that require dynamic phenotyping of single cells with significant heterogeneity.
    Keywords:  extracellular acidification; glycolysis, high‐throughput; microfluidics; phenotyping; single cell
    DOI:  https://doi.org/10.1002/smll.202504687
  30. Sci Adv. 2025 Jun 20. 11(25): eadv7786
      Materials with circumferentially aligned fibers, such as intervertebral discs and arteries, are abundant in nature but challenging to replicate artificially, despite their mechanical advantages. Although ice-templating can create bioinspired materials, the achievable structures remain limited to simple forms, such as honeycomb, lamellar, and radial structures. Here, we developed a unique ice-templating technique that constructs circumferential fibrous structures in hydrogels through slow freezing. Enhanced with rotary compression annealing, these hydrogels exhibit record-breaking features that cannot concurrently be achieved in conventional ice-templated and top-performing tough hydrogels, including high tensile properties, isotropic fatigue threshold of 2320 joules per square meter, ultracompressibility (8% strain after 500 cycles), and extraordinary burst pressure of 1.6 bar while maintaining 85 weight % water content. These properties enable opportunities in robotics, including hydrogel pneumatic grippers and an untethered bioinspired robotic fish that exhibits high-force actuation and long-term robustness. Our approach enriches the diversity of bioinspired structures in artificial materials, establishing exceptional mechanical properties through cross-length scale structural design.
    DOI:  https://doi.org/10.1126/sciadv.adv7786
  31. Mater Horiz. 2025 Jun 17.
      Soft wearable electronics provide a seamless interface between the human body and electronic systems to support real-time, continuous, long-term monitoring in healthcare and other applications. Incorporating mechanically active materials to these soft electronic systems can further expand sensing modalities, enhance sensing performances, and/or enable new functions that are challenging to achieve with physically static electronic devices. A key property of such mechanically active materials is that their shapes can change upon various external stimuli. This review highlights recent advances in this type of material, with a focus on discussing their integration with soft wearable devices and the resulting impact on the performances. Specifically, the content ranges from piezoelectric materials that generate ultrasound and surface acoustic waves, to magnetic materials that allow for new sensing modalities and haptic feedback, and to elastomeric materials that facilitate pneumatic and hydraulic actuation-all designed for soft wearable devices. The review concludes with an analysis of the key challenges and future opportunities for mechanically active materials.
    DOI:  https://doi.org/10.1039/d5mh00563a
  32. Nature. 2025 Jun 18.
      Capturing particles with low, nanonewton-scale adhesion is an ongoing challenge for conventional air filters1,2. Inspired by the natural filtration abilities of mucus-coated nasal hairs3,4, we introduce an efficient, biomimetic filter that exploits a thin liquid coating. Here we show that a stable thin liquid layer is formed on several filter media that generates enhanced particulate adhesion, driven by micronewton to sub-micronewton capillary forces5,6. Enhanced particle adhesion increases the filtration of airborne particulates while maintaining air permeability, providing longer filter lifetime and increased energy savings. Moreover, strong adhesion of the captured particles enables effective filtration under high-speed airflow as well as suppression of particle redispersion. We anticipate that these filters with thin liquid layers afford a new way to innovate particulate matter filtering systems.
    DOI:  https://doi.org/10.1038/s41586-025-09156-y
  33. ACS Appl Mater Interfaces. 2025 Jun 16.
      Degradable hemostatic materials such as gelatin foam are widely used as middle ear packing materials to support tympanic membrane grafts; while safe and biocompatible, such materials have limited mechanical stability when wet. Here, we demonstrate the fabrication of silk-silk composite foams by mixing microfibrillated silk with a low molecular weight silk solution glue to produce water-stable and highly porous foams that retain their structure when wet. The foams exhibited excellent (over 2000%) water absorption, more than 5 times higher than Gelfoam, a commercial hemostatic packing material, and hence higher loading of antibiotics such as ciprofloxacin. Moreover, unlike Gelfoam, ciprofloxacin could be encapsulated into the composite foams during fabrication to produce a dried, off-the-shelf, drug-eluting packing material. This enabled sustained drug release for over 16 days. The addition of microfibers significantly improved shape retention after annealing: samples containing at least a 1:1 mix of silk solution to microfibers showed no shrinkage after annealing, while control foams made from just silk solution shrank by at least 25%. These hybrid foams have immense potential for use as dual-function factor-concentrating hemostatic materials with drug delivery capacity for middle ear packing.
    Keywords:  drug delivery; foam; microfibrillated silk; silk fibroin; surgical packing
    DOI:  https://doi.org/10.1021/acsami.5c10471
  34. ACS Nano. 2025 Jun 18.
      Conventional membrane materials are often limited by their intrinsic shortcomings, including single-functionality, poor environmental adaptability, and insufficient mechanical stability. In recent years, the integration of polymers/hydrogels with solid-state nanochannels (P/H@SSNC) has emerged as a promising strategy to overcome these limitations. Through dynamic pore size regulation, multifunctional interface engineering, and bioinspired design, this approach enables precise ion and molecular manipulation under complex environmental conditions. This Perspective summarizes recent progress in P/H@SSNC integrating stimuli-responsive polymers, three-dimensional network hydrogels, and solid-state nanochannels, which allow for dynamic tuning of pore size and surface chemistry. Furthermore, we highlight the Hofmeister effect as a perspective for ion-specific regulation, where optimizing ion-material interfacial interactions enhances the selectivity and environmental robustness of P/H@SSNC. This strategy facilitates the practical application of intelligent membrane materials in precision medicine, clean energy, and environmental remediation, contributing key technological advancements toward sustainable development.
    Keywords:  Hofmeister Effect; Nanoconfined Effect; Nanofluidic Device; Polymers/Hydrogel; Solid-State Nanochannels
    DOI:  https://doi.org/10.1021/acsnano.5c06303
  35. iScience. 2025 Jun 20. 28(6): 112718
      We developed composite photoresins for sustainable production of microarchitected carbon electrodes via stereolithography (SLA) 3D printing. The composite resins contain 20-25 mass% water that decreases the amount of organic waste. After printing, the scaffolds were pyrolyzed into honeycomb carbon microlattices (hCMLs) at 1,000°C in vacuum. hCMLs show reduced density as the water content increases, inferring subnanoscale structural changes within the constituent carbon. Ni added to photoresin thrusts graphitization at 1,000°C so reduces thermal energy conventional graphitization requires, especially when water delivers individual Ni ions. The homogeneously dispersed Ni ions, in contrast to Ni nanoparticles that aggregate, interconnected graphitized zones in hCMLs to lower electrical resistivity by ∼50%. The Ni-doped hCMLs readily serve as a bifunctional electrocatalyst for water splitting, inspiring design of functional microarchitected carbon composites. Our results can reduce waste and save energy in fabricating carbon microarchitectures, benefitting a wide range of electrical, electrochemical and other applications.
    Keywords:  Applied sciences; Materials science; Natural sciences
    DOI:  https://doi.org/10.1016/j.isci.2025.112718