bims-enlima Biomed News
on Engineered living materials
Issue of 2025–06–01
37 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool
  1. Scaling DNA engineering.
  2. Fibrous polyisocyanide hydrogels for 3D cell culture applications.
  3. Cell-guiding microporous hydrogels by photopolymerization-induced phase separation.
  4. Self-Adjusting Engineered Probiotic for Targeted Tumor Colonization and Local Therapeutics Delivery.
  5. Synthetic Chromatophores for Color and Pattern Morphing Skins.
  6. Engineering Cellular Self-Adhesions Inside 3D Printed Micro-Arches to Enhance Cell:Biomaterial Attachment.
  7. Introduction: Neuromorphic Materials.
  8. Intracellular Formation of Synthetic Peptide Nanostructures Causes Mitochondrial Disruption and Cell Death in Tumor Spheroids.
  9. Pickering Emulsion Biocatalysis with Engineered Living Cells for Degrading Polycarbonate Plastics.
  10. Kinetic modules are sources of concentration robustness in biochemical networks.
  11. Microgels: from synthesis to tissue regeneration applications.
  12. Cancer-fighting immune cells could soon be engineered inside our bodies.
  13. Dynamic Hydrogels with Tunable Mechanics for 3D Organoid Derivation.
  14. Guest Editorial: Structure and mechanics of biofluids, biomaterials, and biologics.
  15. Expansion in situ genome sequencing links nuclear abnormalities to aberrant chromatin regulation.
  16. Designing hydrogel dimensionality to investigate mechanobiology.
  17. Bioinspired, Rapidly Responsive Magnetically Tunable Stiffness Metamaterials.
  18. A photo-mechanically inactive tough gel exhibits multimodal, light-guided underwater navigation.
  19. PISA printing perfusable microcapillaries.
  20. Promoting efficient synthesis and customization of sphingans based on metabolic engineering and synthetic biology strategies.
  21. Materials Horizons 2024 Outstanding Paper Award.
  22. Directed evolution of aminoacyl-tRNA synthetases through in vivo hypermutation.
  23. Nature-Inspired Macromolecular Biocomposites Based on Decellularized Extracellular Matrix.
  24. Adapting OptCouple to Identify Strategies with Increased Product Yields in Community Cohorts of E. coli.
  25. Engineered microbial platform confers resistance against heavy metals via phosphomelanin biosynthesis.
  26. Molecular blueprint of a cellular sorting centre.
  27. From Mechanoelectric Conversion to Tissue Regeneration: Translational Progress in Piezoelectric Materials.
  28. Self-Sufficient and Autosensing Biocatalytic Inks for 3D-Printed Monolithic Bioreactors.
  29. Lipid Nanoparticles for Delivery of CRISPR Gene Editing Components.
  30. Responsive Industrial Polymers: A Marriage of Polyurethanes with Liquid Crystal Elastomers?
  31. Self-packaged stretchable printed circuits with ligand-bound liquid metal particles in elastomer.
  32. Designing Amyloid-Like Protein Aggregates from Microalgal Biomass.
  33. Expression of a RAS Degrader via Synthetic Nanocarrier-Mediated mRNA Delivery Reduces Pancreatic Tumors.
  34. Protein-primed homopolymer synthesis by an antiviral reverse transcriptase.
  35. Unraveling the Impact of Competing Interactions on Nonequilibrium Colloidal Gelation.
  36. Spatiotemporal development of expanding bacterial colonies driven by emergent mechanical constraints and nutrient gradients.
  37. Designing pathways for bioproducing complex chemicals by combining tools for pathway extraction and ranking.
  1. Trends Biotechnol. 2025 May 28. pii: S0167-7799(25)00168-4. [Epub ahead of print]
    Scaling DNA engineering.
    Weiyi Li, Po-Hsiang Hung, Takeshi Matsui, Sasha F Levy, Gavin Sherlock.
      DNA can be engineered to produce new biologics, gene therapies, and cellular therapies, and to reprogram organisms. Having the ability to engineer DNA at scale can accelerate the development of these applications. Existing technologies excel at short oligonucleotide synthesis by chemical or enzymatic methods (up to 2000 bp) and intermediate-size DNA assembly (up to 5-7 kb). Yet synthesizing sequence-validated longer DNA (>10 kb) and/or constructing highly complex combinatorial DNA libraries at scale remains a significant challenge, due largely to technical and cost barriers. Inspired by recent studies on an in vivo DNA processing platform for megabase-long DNA assembly and on high-throughput sequence verification, we discuss how these platforms may be used to achieve DNA engineering at scale.
    Keywords:  DNA assembly; bacterial conjugation; homologous recombination
    DOI:  https://doi.org/10.1016/j.tibtech.2025.05.002
  2. Nat Protoc. 2025 May 30.
    Fibrous polyisocyanide hydrogels for 3D cell culture applications.
    Hongbo Yuan, Kaizheng Liu, Melissa J J van Velthoven, Jyoti Kumari, Yuying Bao, Susana Rocha, Paul H J Kouwer.
      Three-dimensional (3D) cell culture models based on hydrogels are rapidly evolving into a prominent tool for tissue engineering, mechanobiology, disease modeling and drug screening. While a vast variety of synthetic gels have emerged in recent years, they fail to penetrate the market substantially for two major reasons: they poorly mimic the extracellular matrix or they are difficult to use in gel formation and cell extraction. Mimicking the complexity of nature is challenging: the extracellular matrix plays a crucial role in cell development and function, which goes well beyond simple mechanical support. Recently, we introduced polyisocyanide (PIC) hydrogels for 3D cell culture applications. The fibrous architecture and associated (non)linear mechanical behavior closely mimic the physical properties of biogels such as collagen and fibrin. As fully synthetic materials, PIC gels benefit from high tailorability and reproducibility. Moreover, the thermoresponsive properties of PIC gels make them easy to handle in the lab; the gels form instantly at 37 °C and cells are easily extracted after cooling to 5 °C. The potential of PIC gels has been demonstrated in a quickly expanding library of papers discussing different cell lines, primary cells and organoids, as well as in vivo experiments. This manuscript provides protocols on how to handle PIC gels in the chemistry and cell biology laboratories. Material preparation requires 72 h. Cell encapsulation takes 1 h and the time for downstream analysis depends on the (commercial) methods used. The protocols described are suitable for researchers with expertise in cell culture and molecular biology.
    DOI:  https://doi.org/10.1038/s41596-025-01159-3
  3. Nat Commun. 2025 May 27. 16(1): 4923
    Cell-guiding microporous hydrogels by photopolymerization-induced phase separation.
    Monica Z Müller, Margherita Bernero, Chang Xie, Wanwan Qiu, Esteban Oggianu, Lucie Rabut, Thomas C T Michaels, Robert W Style, Ralph Müller, Xiao-Hua Qin.
      Microporous scaffolds facilitate solute transport and cell-material interactions, but materials allowing for spatiotemporally controlled pore formation in aqueous solutions are lacking. Here, we propose cell-guiding microporous hydrogels by photopolymerization-induced phase separation (PIPS) as instructive scaffolding materials for 3D cell culture. We formulate a series of PIPS resins consisting of two ionic polymers (norbornene-functionalized polyvinyl alcohol, dextran sulfate), di-thiol linker and water-soluble photoinitiator. Before PIPS, the polymers are miscible. Upon photocrosslinking, they demix due to the increasing molecular weight and form a microporous hydrogel. The pore size is tunable in the range of 2-40 μm as a function of light intensity, polymer composition and molecular charge. Unlike conventional methods to fabricate porous hydrogels, our PIPS approach allows for in situ light-controlled pore formation in the presence of living cells. We demonstrate that RGD-functionalized microporous hydrogels support high cell viability (>95%), fast cell spreading and 3D morphogenesis. As a proof-of-concept, these hydrogels also enhance the osteogenic differentiation of human mesenchymal stromal cells, matrix mineralization and collagen secretion. Collectively, this study presents a class of cell-guiding microporous hydrogels by PIPS which may find applications in complex tissue engineering.
    DOI:  https://doi.org/10.1038/s41467-025-60113-9
  4. Adv Sci (Weinh). 2025 May 28. e06486
    Self-Adjusting Engineered Probiotic for Targeted Tumor Colonization and Local Therapeutics Delivery.
    Zhen-Ping Zou, Xin-Ge Wang, Xuan-Ren Shi, Shu-Ting Sun, Jing Mi, Xiao-Peng Zhang, Bin-Cheng Yin, Ying Zhou, Bang-Ce Ye.
      Engineered bacteria have demonstrated great potential for treating a broad array of tumors. However, the precision and safety of controlling the performance of engineered bacteria in vivo remains a central challenge. Here, genetic circuit programming strategy is utilized to construct an engineered Escherichia coli Nissle 1917 with accurate targeted colonizing and on-demand payloads releasing ability. The engineered probiotic survives only in the presence of more than 5 mM L-lactate by employing an improved lactate-sensing system, which leads to preventing the growth outside the permissive environments in mice. Meanwhile an expressing α-hemolysin (SAH) circuit based on quorum-sensing system is introduced to augment anti-tumor effect. Furthermore, coagulase (Coa) induced by high-level lactate creates the closure to deprive tumor of nutrients and oxygen and may help prevent the leakage of bacteria and SAH, which enhances the therapeutic effectiveness and biosafety. This self-adjusting living biotherapeutics significantly inhibits tumor proliferation and prolongs the survival time of colorectal tumor-bearing mice. Together, this work takes a step toward safer and more effective application of living bacteria for tumor treatment in practice.
    Keywords:  engineered probiotics; multiplexed; self‐adjusting; synthetic biology; tumors treatment
    DOI:  https://doi.org/10.1002/advs.202406486
  5. Adv Mater. 2025 May 24. e2505104
    Synthetic Chromatophores for Color and Pattern Morphing Skins.
    Brennan P Watts, Matthew R Jamison, John M Kapitan, Nengjian Huang, Delroy Taylor, Stephen A Morin.
      The dynamic optical and mechanical properties of cephalopod skin cannot be mimicked using traditional display technologies. Soft materials (and systems thereof) have the potential to realize cephalopod-like color switching capabilities synthetically. This report describes the fabrication of stretchable arrays of microstructured, stimuli-responsive hydrogels, "synthetic chromatophores," that emulate the mechano-dynamic action of color change found in cephalopods. By combining multiple layers of these synthetic chromatophores, soft skins with color and pattern morphing capabilities that leverage halftone absorption, optical interference, and microlensing are demonstrated. These skins, made entirely of soft materials, are inherently stretchable and can be programmed to respond to specific environmental stimuli, making them well-suited for applications in soft robotics and human-machine interfaces.
    Keywords:  chromatophores; halftones; hydrogels; microactuation; microlens; moire interference
    DOI:  https://doi.org/10.1002/adma.202505104
  6. Adv Mater. 2025 May 24. e2502425
    Engineering Cellular Self-Adhesions Inside 3D Printed Micro-Arches to Enhance Cell:Biomaterial Attachment.
    Anamika Singh, Hannah E Kim, Lauren Rawson, Margaret Miao, Daniel J Cohen.
      A cell can bind to itself and form a self-adhesion that can be engineered and harnessed as a new way to adhere cells to engineered materials-a key challenge for biomaterials are demonstrated. Here, a 3D structure smaller is developed than a single cell, that a Self-Adhesion-Tunnel (SAT) is called, that causes cells to wrap around it and bind to themselves. This process is driven through the cadherin proteins that regulate cell-cell adhesion, and it is shown that many of the key elements of a normal cell-cell adhesion are found in self-adhesions. Size and shape of the SAT determine the efficiency of self-adhesion formation, and >90% efficient formation of self-adhesions are observed in both kidney and skin cells per SAT. Self-adhesions can persist for at least 24 hrs and act to stabilize the cell-material interface and reduce migration. Overall, this ability to co-opt the native cell-cell adhesion machinery in cells and use it as an attachment strategy can provide new approaches for soft-tissue implant integration and tissue engineering scaffolds where stable tissue-material interfaces are critical.
    Keywords:  Biomaterials; bioprinting; cell adhesion; nanomaterials; two photon
    DOI:  https://doi.org/10.1002/adma.202502425
  7. Chem Rev. 2025 May 28. 125(10): 4765-4767
    Introduction: Neuromorphic Materials.
    A Alec Talin, Bilge Yildiz.
      
    DOI:  https://doi.org/10.1021/acs.chemrev.5c00340
  8. Adv Sci (Weinh). 2025 May 26. e2412606
    Intracellular Formation of Synthetic Peptide Nanostructures Causes Mitochondrial Disruption and Cell Death in Tumor Spheroids.
    Sarah Chagri, Konrad Maxeiner, Maria J S A Silva, Lisa Förch, Julian Link, Patrick Roth, Raphael Meyer, Jana Fetzer, Anke Kaltbeitzel, Ingo Lieberwirth, Katharina Landfester, Manfred Wagner, David Y W Ng, Tanja Weil.
      Supramolecular assemblies found in nature demonstrate the concept of creating functionality through structure formation. In recent years, these complex natural architectures have inspired the development of materials for the formation of synthetic nanostructures within living cells. These intracellular assemblies have the potential to modulate cellular processes, yet their specific effects on cellular metabolism and 3D cell networks, such as tumor spheroids, still remain underexplored. Herein, the study correlates the glutathione-induced formation of synthetic nanostructures inside MDA-MB-231 triple-negative breast cancer cells to the metabolic disruption and mitochondrial degradation observed in 2D cell culture, as well as to cell death and size decrease in a 3D tumor spheroid model. In 2D cell culture, material-cell interactions are examined through live-cell imaging and by quantifying changes in mitochondrial respiration. By studying the interplay between glutathione-responsive cytosolic peptide assembly and the implications on the integrity of the mitochondrial network, as well as on 3D cell networks, the work advances the understanding of how synthetic intracellular nanofibers impact vital functions of living cells.
    Keywords:  bioresponsive nanomaterials; mitochondrial disruption; peptide nanostructures; supramolecular assemblies; synthetic intracellular nanostructures; tumor spheroids
    DOI:  https://doi.org/10.1002/advs.202412606
  9. Small. 2025 May 24. e2504376
    Pickering Emulsion Biocatalysis with Engineered Living Cells for Degrading Polycarbonate Plastics.
    Shan Wang, Zhimin Gong, René Hübner, Henrik Karring, Changzhu Wu.
      The efficient degradation of plastics remains a pressing environmental challenge due to their inherent resistance to breakdown. While biocatalysis offers a promising approach for sustainable and effective plastic degradation, the inherently low solubility of plastics in aqueous systems severely limits the efficiency of enzymatic reactions. To address this issue, we developed a biocompatible polymer coating strategy to engineer living cell surfaces, enabling the stabilization of Pickering emulsions for over 192 h and significantly enhancing plastic accessibility to biocatalysts. Leveraging this platform, Escherichia coli (E. coli) cells containing overexpressed Candida antarctica Lipase B performed well by dispersing at the emulsion interface of water and toluene, facilitating the efficient biodegradation of polycarbonate (PC) plastics. Under optimized reaction conditions (pH 9, 45 °C), this Pickering emulsion system achieved efficient PC degradation, producing up to 4.5 mm bisphenol A within 72 h-far exceeding the performance of biphasic systems using native E. coli cells. The findings highlight the transformative potential of surface-engineered whole-cell catalysts in addressing environmental challenges, particularly plastic waste remediation.
    Keywords:  interfacial catalysis; pickering emulsion; plastic degradation; polymeric coating; whole‐cell
    DOI:  https://doi.org/10.1002/smll.202504376
  10. Sci Adv. 2025 May 30. 11(22): eads7269
    Kinetic modules are sources of concentration robustness in biochemical networks.
    Damoun Langary, Anika Küken, Zoran Nikoloski.
      Modules represent fundamental building blocks of cellular networks and are thought to facilitate robustness of phenotypes against perturbations. While reaction kinetic shapes the concentration of components and reaction rates, its use in identification of modules entails knowledge of parameter values. Here, we demonstrate that kinetic modules can be efficiently identified on the basis of steady-state reaction rate couplings in large-scale biochemical networks endowed with mass action kinetics without knowledge of parameter values. We then link the kinetic modules of metabolic networks with robustness of metabolite concentrations to perturbations. Analyzing 34 metabolic network models of 26 organisms, we demonstrate that the ordered binding enzyme mechanism leads to increased concentration robustness compared to random binding. Our findings pave the way for usage of modules in synthetic biology and biotechnological applications.
    DOI:  https://doi.org/10.1126/sciadv.ads7269
  11. Biofabrication. 2025 May 28.
    Microgels: from synthesis to tissue regeneration applications.
    Sung Yun Hann, Yunsung Kang, Haitao Cui, Lijie Grace Zhang.
      Microgels have emerged as a versatile platform in tissue engineering and regenerative medicine, offering unique physicochemical properties, modularity, and the ability to mimic native extracellular matrix (ECM) microenvironments. Derived from natural or synthetic hydrogels, microgels exhibit biocompatibility, controllability, and injectability, which make them suitable for diverse tissue engineering applications. This review systematically explores the fabrication methods of microgels and highlights their role in cell encapsulation, therapeutic delivery, and structural tissue development. Advanced strategies in microgel manufacturing, such as injectable hydrogels, assembled microgel platforms, and in-gel assemblies, have enabled the creation of highly customizable and functional tissue constructs. Additionally, 3D bioprinting of microgels provides a high-throughput strategy to generate patient-specific scaffolds with precise spatial organization and enhanced cellular viability. Recent innovations, including stimuli-responsive and four-dimensional (4D) microgels, further expand their potential by enabling dynamic in situ tunable microenvironments. It is expected that more efficient and cost-effective strategies for mass production and customization of microgel systems to specific cell types or patient needs are essential for future studies. These advancements will enable optimal design, scalability, and integration into therapeutic applications, thereby accelerating the clinical translation of microgel-based therapies and driving the development of multifunctional tissue products.&#xD.
    Keywords:  3D bioprinting; Assembly; Cell encapsulation; Injectable hydrogels; Tissue Regeneration
    DOI:  https://doi.org/10.1088/1758-5090/addde9
  12. Nature. 2025 May;641(8065): 1090-1092
    Cancer-fighting immune cells could soon be engineered inside our bodies.
    Cassandra Willyard.
      
    Keywords:  Cancer; Drug discovery; Health care; Molecular biology; Nanoparticles
    DOI:  https://doi.org/10.1038/d41586-025-01570-6
  13. Small. 2025 May 28. e2501862
    Dynamic Hydrogels with Tunable Mechanics for 3D Organoid Derivation.
    Xueyong Xie, Xuewen Chen, Jian Zhou, Tiansong Wang, Gen Yang, Fei Han, Zhao Wei.
      The mechanical properties of the hydrogel play a pivotal role in governing the formation and development of 3D organoids in vitro. However, commonly employed natural hydrogels, such as Matrigel and other extracellular matrix (ECM)-derived products, are characterized by ill-defined and complex compositions, resulting in non-tunable mechanical properties. This limitation poses challenges in controlling organoids' developmental trajectory and 3D morphology. Although numerous synthetic hydrogels with well-defined chemical structures have recently been adopted to study organoids by modulating stiffness, advanced research emphasizes the importance of dynamic mechanical cues, such as dynamic stiffness softening and dynamic viscoelasticity, for optimal organoid derivation. These cues are essential for mimicking the dynamic physiological states of organoids during their growth. Despite their potential, the concept of dynamic hydrogels is often used interchangeably, and a systematic review is lacking to clarify this ambiguity. Furthermore, the mechanisms through which dynamic mechanical cues regulate organoid formation have not been thoroughly reported. This review endeavors to summarize and categorize dynamic hydrogels and reveal the effects of dynamic mechanics on organoid derivation. Additionally, the prospects of dynamic hydrogels in organoid derivation are deliberated to promote a more rational design of synthetic hydrogels, guiding organoid derivation and propelling organoid technology in biomedicine.
    Keywords:  3D organoid derivation; dynamic hydrogels; dynamic softening hydrogels; dynamic viscoelastic hydrogels; tunable mechanics
    DOI:  https://doi.org/10.1002/smll.202501862
  14. APL Bioeng. 2025 Jun;9(2): 020401
    Guest Editorial: Structure and mechanics of biofluids, biomaterials, and biologics.
    E M Furst, F Scheffold, G H McKinley.
      
    DOI:  https://doi.org/10.1063/5.0274572
  15. Science. 2025 May 29.
    Expansion in situ genome sequencing links nuclear abnormalities to aberrant chromatin regulation.
    Ajay S Labade, Zachary D Chiang, Caroline Comenho, Paul L Reginato, Andrew C Payne, Andrew S Earl, Rojesh Shrestha, Fabiana M Duarte, Ehsan Habibi, Ruochi Zhang, George M Church, Edward S Boyden, Fei Chen, Jason D Buenrostro.
      Microscopy and genomics are used to characterize cell function, but approaches to connect the two types of information are lacking, particularly at subnuclear resolution. Here, we describe expansion in situ genome sequencing (ExIGS), a technology that enables sequencing of genomic DNA and superresolution localization of nuclear proteins in single cells. Applying ExIGS to progeria-derived fibroblasts revealed that lamin abnormalities are linked to hotspots of aberrant chromatin regulation that may erode cell identity. Lamin was found to generally repress transcription, suggesting variation in nuclear morphology may affect gene regulation across tissues and aged cells. These results demonstrate that ExIGS may serve as a generalizable platform to link nuclear abnormalities to gene regulation, offering insights into disease mechanisms.
    DOI:  https://doi.org/10.1126/science.adt2781
  16. Soft Matter. 2025 May 29.
    Designing hydrogel dimensionality to investigate mechanobiology.
    Marine Luciano, Sylvain Gabriele.
      Hydrogels are indispensable tools for mechanobiology, providing tunable platforms that mimic the complex extracellular matrix and facilitate the study of cell-microenvironment interactions. This review highlights recent advances in the design of hydrogel systems with dimensionality ranging from 2D to 3D, including innovative 2.5D and sandwich configurations, to dissect the role of biophysical cues in cellular behavior and phenotype regulation. Special attention is given to alginate and gelatin methacrylamide (GelMA) hydrogels, which offer unique mechanical and biochemical properties tailored for diverse applications in 3D cell culture. Cutting-edge strategies to dynamically modulate hydrogel stiffness, viscoelasticity, and spatial confinement are discussed, showcasing their impact on cancer progression, stem cell differentiation, and collective cell migration. By integrating advanced hydrogel fabrication methods, including photopolymerization, dual cross-linking, and microfabrication techniques, this review underscores the transformative potential of hydrogels for unraveling the complexities of cellular mechanotransduction in evolving environments. We also explore the clinical potential of engineered hydrogels across applications including tissue regeneration, disease modeling, and controlled drug delivery. Finally, we discussed key challenges in replicating the dynamic mechanical complexity of living tissues and highlight emerging opportunities in the development of smart and adaptive hydrogel systems. Together, these innovations are paving the way toward next-generation biomimetic platforms that bridge fundamental research and translational applications in mechanobiology.
    DOI:  https://doi.org/10.1039/d4sm01458h
  17. Adv Mater. 2025 May 27. e2505880
    Bioinspired, Rapidly Responsive Magnetically Tunable Stiffness Metamaterials.
    Gooyoon Chung, Huy Le Quang, Jung Hyun Kim, Jeongmin Yoo, Seung Kwon Seol, Yoonseok Park.
      Programmable mechanical materials often require dynamic stiffness adaptability, but existing solutions face challenges with slow response times and limited precision. This study introduces magnetically tunable stiffness metamaterials (MTSM) that utilize a bioinspired ternary programming framework to achieve rapid and precise stiffness modulation. Drawing inspiration from biological sarcomeres, which naturally adjust stiffness through structural changes, the MTSM design employs direct ink writing, a 4D printing method, to incorporate neodymium microparticles and a styrene-isoprene-styrene polymer matrix. This approach enables the metamaterial to transition between three distinct stiffness states-soft, moderate, and stiff-through structural deformation controlled by magnetic torque. Integration of MTSM into a 3D array further enhances its versatility, allowing multi-layer stiffness adjustments under magnetic fields. The MTSM array achieves an impressive 390 percent stiffness modulation range and rapid changes in response to an external magnetic field, surpassing the limitations of prior designs. These findings emphasize the potential of ternary programming in MTSM as a foundation for creating next-generation programmable mechanical systems capable of rapid and efficient adaptability.
    Keywords:  4D printing; active mechanical metamaterials; bioinspired; stimuli‐responsive materials; ternary programming; tunable stiffness
    DOI:  https://doi.org/10.1002/adma.202505880
  18. Sci Adv. 2025 May 30. 11(22): eads4507
    A photo-mechanically inactive tough gel exhibits multimodal, light-guided underwater navigation.
    Guodong Hou, Xuning Wang, Feiyu Zhang, Wei Lu, Xin Chen, Tiannan Yang, Guang Meng, Xiaoshi Qian.
      Soft robots exhibit flexural and active features that enabled their potential deployment in applications where rigid systems could not perform well. However, the locomotion of the soft robots still largely relies on the paddling that requires variety of active materials as artificial muscles. Hence, extreme conditions, i.e., under compressive or tensile loads, can cause irreversible damages that disable the actuation. Here, we report a tough underwater robot that exhibits an accurate, three-dimensional, and multimodal motion. Counterintuitively, the soft robot is composed of polymers that are not photo-mechanically responsive but are powered by the ambient fluid. The unique feature notably widens the pool of material selection and allows further treatment to strengthen the polymer matrix without concerns of trade-off between the mechanical properties with the actuation capability. The tough, photo-inactive gel maneuvers precisely, traveling effortlessly in and out of the tunnels, and enables versatile phototactic locomotion.
    DOI:  https://doi.org/10.1126/sciadv.ads4507
  19. Biomater Sci. 2025 May 27.
    PISA printing perfusable microcapillaries.
    Aaron Priester, Jimmy Yeng, Yuwei Zhang, David Christofferson, Risheng Wang, Anthony J Convertine.
      Polymerization-induced self-assembly (PISA) printing combines reversible addition-fragmentation chain transfer (RAFT) polymerization with digital light projection (DLP) photolithography to create high-resolution three-dimensional structures without permanent covalent crosslinks. Here, we intoduce a simplified, one-pot, purification-free synthesis for multi-chain transfer agent (multi-CTA) scaffolds that spontaneously form robust physical networks durnig printing, stabilized by interparticle bridges and knots. By tuning solvent-resin chemistry and polymer composition, we achieved precise control over nanoscale morphologies and selective distribution behaviors. This approach was demonstrate through successful fabrication of perfusable microvascular networks and open-channel polydimethylsiloxane (PDMS) microfluidic devices, where sacrificial scaffolds dissolved cleanly to yield stable microchannels. Collectively, these findings enhance the accessibliity, flexibility, and functionality of PISA printing, offering an efficient and adaptable platform for microfabrication, rapid prototyping, and advance d tissue engineering applications.
    DOI:  https://doi.org/10.1039/d5bm00547g
  20. Carbohydr Polym. 2025 Sep 01. pii: S0144-8617(25)00517-X. [Epub ahead of print]363 123734
    Promoting efficient synthesis and customization of sphingans based on metabolic engineering and synthetic biology strategies.
    Yujia Zhou, Jielun Hu, Yadong Zhong, Shaoping Nie.
      Sphingans are important exopolysaccharides due to their unique functional characteristics and potential application prospects in various fields. In recent years, the chemical structure, biosynthesis and function of sphingans have been studied extensively. With the development of metabolic engineering and synthetic biology, problems that restricting the production capacity and the design of sphingans, such as complex synthetic path and unclear research background of the wildtype strain, would be expected to be solved to some extent. This review describes the structure and biosynthetic pathways of different sphingans, analyzes the feasibility of obtaining high-performance sphingans-producing strains via classical mutagenesis combined with high-throughput screening techniques and chassis cells construction, and focuses on discussing how to efficiently synthesize and customize sphingans based on metabolic engineering and synthetic biology strategies. These strategies include using highly effective tools like genomic metabolic network models (GSMM) and CRISPR to regulate metabolic pathways, as well as customizing sphingans with different molecular weight through molecular weight regulation and controllable substituent modification based on genetic engineering. At last, the main challenges and prospects are discussed.
    Keywords:  Custom synthesis; Genome-scale metabolic network model; Metabolic engineering; Mutagenesis; Sphingans; Synthetic pathway
    DOI:  https://doi.org/10.1016/j.carbpol.2025.123734
  21. Mater Horiz. 2025 May 29.
    Materials Horizons 2024 Outstanding Paper Award.
      
    DOI:  https://doi.org/10.1039/d5mh90051d
  22. Nat Commun. 2025 May 24. 16(1): 4832
    Directed evolution of aminoacyl-tRNA synthetases through in vivo hypermutation.
    Yuichi Furuhata, Gordon Rix, James A Van Deventer, Chang C Liu.
      Genetic code expansion (GCE) is a critical approach to the site-specific incorporation of non-canonical amino acids (ncAAs) into proteins. Central to GCE is the development of orthogonal aminoacyl-tRNA synthetase (aaRS)/tRNA pairs wherein engineered aaRSs recognize chosen ncAAs and charge them onto tRNAs that decode blank codons (e.g., the amber stop codon). However, evolving new aaRS/tRNA pairs traditionally relies on a labor-intensive process that often yields aaRSs with suboptimal ncAA incorporation efficiencies. Here, we present an OrthoRep-mediated strategy for aaRS evolution, which we demonstrate in 8 independent aaRS evolution campaigns, yielding multiple aaRSs that incorporate an overall range of 13 ncAAs tested. Some evolved systems enable ncAA-dependent translation at single amber codons with similar efficiency as natural translation at sense codons. Additionally, we discover an aaRS that regulated its own expression to enhance ncAA dependency. These findings demonstrate the potential of OrthoRep-driven aaRS evolution platforms to advance the field of GCE.
    DOI:  https://doi.org/10.1038/s41467-025-60120-w
  23. Macromol Rapid Commun. 2025 May 26. e2401049
    Nature-Inspired Macromolecular Biocomposites Based on Decellularized Extracellular Matrix.
    Yihan Lin, Yuting Lin, Haohua Hu, Panqin Ma, Zheng Luo, Gang Tan, Yun-Long Wu.
      Extracellular matrix (ECM) is a multifaceted network that encases cells, composed of various polysaccharides, proteins, and adhesion molecules, etc. It plays a critical role in providing structural support to cells and regulating essential cellular activities such as proliferation, migration, and differentiation. Due to these functions, decellularized extracellular matrix (dECM) has attracted considerable interest in biomedicine and holds promising application potential. However, simple dECM materials are often insufficient to meet the diverse demands of different physiological or pathological microenvironments. Recently, composite materials made from biomaterials and dECM have emerged as a solution, significantly enhancing the biological functions and clinical applicability of dECM. By using different material preparation techniques, these composite materials can be endowed with specific properties, enabling them to better meet the requirements of various biomedical applications. In this review, the preparation techniques for various dECM-based composite biomaterials, including physical crosslinking, chemical modification, 3D printing, and electrospinning, are summarized. Different types of dECM-based composites are also classified, and their biological and material properties are discussed, highlighting their suitability for specific biomedical applications. This review aims to provide a comprehensive reference for the development and clinical translation of dECM-based biomaterials, from preparation to application.
    Keywords:  biomaterials; biomedical applications; clinical translation; composites; decellularized extracellular matrix
    DOI:  https://doi.org/10.1002/marc.202401049
  24. Metabolites. 2025 May 06. pii: 309. [Epub ahead of print]15(5):
    Adapting OptCouple to Identify Strategies with Increased Product Yields in Community Cohorts of E. coli.
    Nicole Pearcy, Jamie Twycross.
       BACKGROUND: Microbesas chemical factories provide an alternative sustainable approach for producing platform chemicals. Until recently, most efforts have involved engineering heterologous pathways into a single microbial chassis to maximise its production of a target chemical. More recently, cohorts of microbes have been used to engineer microbial communities to achieve higher yields than achieved in a single chassis.
    Keywords:  OptCouple; community microbial designs; guaranteed product yields; multi-directional dependent models
    DOI:  https://doi.org/10.3390/metabo15050309
  25. Nat Commun. 2025 May 24. 16(1): 4836
    Engineered microbial platform confers resistance against heavy metals via phosphomelanin biosynthesis.
    Xiaokang Ren, Luyang Zhao, Jintao Shen, Peng Zhou, Kaili Zhao, Chengqian Yuan, Ruirui Xing, Xuehai Yan.
      Environmental concerns are increasingly fueling interest in engineered living materials derived from microbial sources. Melanin biosynthesis in microbes, particularly facilitated by recombinant tyrosinase expression, offers sustainable protection for the habitat of microorganisms against severe environmental stressors. However, there exists a vast urgency to optimize these engineered microbial platforms, which will amplify their protective capabilities, integrate multifaceted functions, and thereby expand their utility and effectiveness. Here, we genetically engineer microbial platforms capable of endogenously biosynthesizing phosphomelanin, a unique phosphorus-containing melanin. The ability to heterogeneously biosynthesize phosphomelanin endows the microbes with enhanced resistance to heavy metals, thus safeguarding their survival in adverse conditions. Furthermore, we upgrade these engineered microbes by integrating PET-degrading enzymes, thereby achieving effective integrated management of metallized plastic waste. This engineered microbial platform, with its phosphomelanin biosynthetic capabilities, presents significant opportunities for microbes to engage in bioengineering manufacturing, potentially serving as the next-generation guardians against global ecological challenges.
    DOI:  https://doi.org/10.1038/s41467-025-60117-5
  26. Nature. 2025 May 28.
    Molecular blueprint of a cellular sorting centre.
      
    Keywords:  Biological techniques; Cell biology; Computational biology and bioinformatics
    DOI:  https://doi.org/10.1038/d41586-025-01564-4
  27. Adv Mater. 2025 May 28. e2417564
    From Mechanoelectric Conversion to Tissue Regeneration: Translational Progress in Piezoelectric Materials.
    Xinyu Wang, Sílvio Terra Stefanello, Victor Shahin, Yun Qian.
      Piezoelectric materials, capable of converting mechanical stimuli into electrical signals, have emerged as promising tools in regenerative medicine due to their potential to stimulate tissue repair. Despite a surge in research on piezoelectric biomaterials, systematic insights to direct their translational optimization remain limited. This review addresses the current landscape by bridging fundamental principles with clinical potential. The biomimetic basis of piezoelectricity, key molecular pathways involved in the synergy between mechanical and electrical stimulation for enhanced tissue regeneration, and critical considerations for material optimization, structural design, and biosafety is discussed. More importantly, the current status and translational quagmire of mechanisms and applications in recent years are explored. A mechanism-driven strategy is proposed for the therapeutic application of piezoelectric biomaterials for tissue repair and identify future directions for accelerated clinical applications.
    Keywords:  advanced materials for translational medicine; biosensors; piezoelectricity; regenerative medicine; tissue engineering
    DOI:  https://doi.org/10.1002/adma.202417564
  28. ACS Appl Mater Interfaces. 2025 May 25.
    Self-Sufficient and Autosensing Biocatalytic Inks for 3D-Printed Monolithic Bioreactors.
    Daniel Andrés-Sanz, Clara García-Astrain, Uxue Aizarna-Lopetegui, Elisa Lenzi, Dorleta Jimenez de Aberasturi, Fernando López-Gallego.
      Additive manufacturing, commonly known as three-dimensional (3D) printing, transforms simple in silico designs into real objects with accessibility, reproducibility, and precision. By merging the versatility of 3D printing with the inherent advantages of enzymatic processes, this technology opens up new possibilities for optimizing enzyme immobilization in continuous flow reactors. Here, we systematically investigate various formulations to develop an optimal biocatalytic ink capable of encapsulating enzymes and cofactors within a hydrogel matrix. The ink, composed of agarose and polyethylenimine (PEI), printed as porous monoliths, improved enzyme retention and cofactor absorption through ionic interactions, outperforming alternative formulations. By further integrating gold nanorods into the system, reaction substrates and intermediates (i.e., NAD+, isopropanol) can be detected through in operando surface enhanced Raman scattering (SERS) sensing, serving as a complementary tool for fluorescence microscopy. Using this optimized ink, we fabricated 3D-printed reactors with diverse architectures to evaluate their efficiency in the continuous flow reduction of ethyl acetoacetate. Reactors with a cross-shaped design exhibit stable product yields and minimize enzyme and cofactor leaching during continuous operation. Hence, we formulate and print a self-sufficient biocatalytic ink capable of sustaining the activity of immobilized dehydrogenases in continuous flow reactions without the addition of exogenous cofactors.
    Keywords:  3D printing; NAD(P)H recycling; SERS; biocatalytic ink; dehydrogenases; flow biocatalysis
    DOI:  https://doi.org/10.1021/acsami.5c03485
  29. Small Methods. 2025 May 28. e2401632
    Lipid Nanoparticles for Delivery of CRISPR Gene Editing Components.
    Fan Wu, Nei Li, Yudian Xiao, Rohan Palanki, Hannah Yamagata, Michael J Mitchell, Xuexiang Han.
      Gene editing has emerged as a promising therapeutic option for treating genetic diseases. However, a central challenge in the field is the safe and efficient delivery of these large editing tools, especially in vivo. Lipid nanoparticles (LNPs) are attractive nonviral vectors due to their low immunogenicity and high delivery efficiency. To maximize editing efficiency, LNPs should efficiently protect gene editing components against multiple biological barriers and release them into the cytoplasm of target cells. In this review, the widely used CRISPR gene editing systems are first overviewed. Then, each component of LNPs, as well as their effects on delivery, are systematically discussed. Following this, the current LNP engineering strategies to achieve non-liver targeting are summarized. Finally, preclinical and clinical applications of LNPs for in vivo genome editing are highlighted, and perspectives for the future development of LNPs are provided.
    Keywords:  delivery; gene editing; gene therapy; lipid nanoparticles
    DOI:  https://doi.org/10.1002/smtd.202401632
  30. ACS Appl Mater Interfaces. 2025 May 26.
    Responsive Industrial Polymers: A Marriage of Polyurethanes with Liquid Crystal Elastomers?
    Lansong Yue, Xue Wan, Tankut Türel, Albert P H J Schenning, Željko Tomović, Michael G Debije.
      Responsive polymers have yet to significantly impact the marketplace. In this Perspective, we offer a glimpse of a possible future industrial-scale responsive polymer. We begin by briefly reviewing two different existing polymer materials, one with high volume, excellent processability, and commercial impact (polyurethanes), the other with stimuli responsive functional properties (liquid crystal elastomers). We explore the possibilities of combining the properties of these two disparate entities into a single material. We offer intriguing possibilities for a bulk polymer with both responsivity and processability that could compete in the market with the long-established residents and discuss some of the research roadblocks that need to be overcome to reach this lofty goal.
    Keywords:  industrial polymers; liquid crystal elastomers; polyurethanes; smart materials; stimuli-responsive actuators
    DOI:  https://doi.org/10.1021/acsami.5c09198
  31. Nat Commun. 2025 May 28. 16(1): 4944
    Self-packaged stretchable printed circuits with ligand-bound liquid metal particles in elastomer.
    Hyeonyeob Seo, Gun-Hee Lee, Jiwoo Park, Dong-Yeong Kim, Yeonzu Son, Semin Kim, Kum Seok Nam, Congqi Yang, Joonhee Won, Jae-Young Bae, Hyunjun Kim, Seung-Kyun Kang, Steve Park, Jiheong Kang, Seongjun Park.
      Packaging in stretchable electronics is crucial to protect components from environmental damage while preserving mechanical flexibility and providing electrical insulation. The conventional packaging process involves multiple steps that increase in complexity as the number of circuit layers multiply. In this study, we introduce a self-packaged stretchable printed circuit board enabled by the in situ phase separation of liquid metal particles (LMPs) within various polymer matrices during solution-based printing processes. The ligand-bound LMPs (LB-LMPs), engineered to inhibit oxide growth, undergo in situ sintering, prompting vertical phase separation. This synthesis strategy not only achieves high initial conductivity of the LMPs but also encapsulates them within the polymer matrix, preventing leakage and providing electrical insulation. Our method enables multi-layer circuit printing, eliminating the need for additional activation and packaging processes. Furthermore, by integrating conductive materials into packaging layers for selective electrical conductivity, vertical interconnect accesses and conductive pads can be formed, enabling large-scale, stretchable, and leakage-free multi-layer electrical circuits and bio-interfaces.
    DOI:  https://doi.org/10.1038/s41467-025-60118-4
  32. Biomacromolecules. 2025 May 28.
    Designing Amyloid-Like Protein Aggregates from Microalgal Biomass.
    Yidan Wen, Andrea Petkovic, Juliana Vicente, John Allingham, Kevin De France.
      Our societal dependence on petrochemical-derived plastics has significant environmental ramifications, with about 80% of such plastics ending up as persistent waste. To this end, we investigate the extraction and purification of proteins from microalgae, specifically spirulina and chlorella, and their self-assembly into amyloid-like aggregates as building blocks toward the development of sustainable bioplastic materials. After self-assembly, spirulina proteins formed beta-sheet-rich structures with a typical (albeit short and worm-like) fibrillar morphology, while chlorella proteins predominantly aggregated into nonfibrillar, spherical/annular structures. Despite their morphological differences, both microalgal protein aggregates exhibited impressive stability across a wide pH range, persisting up to pH 11 before disaggregating at pH 12. In short, this work highlights the importance of biomass source, protein purity, and composition on the aggregation process of differing proteins. Given the high protein content and expanding industrial production of microalgae, spirulina and chlorella present an untapped resource for the development of sustainable bioplastics.
    DOI:  https://doi.org/10.1021/acs.biomac.5c00192
  33. ACS Appl Bio Mater. 2025 May 29.
    Expression of a RAS Degrader via Synthetic Nanocarrier-Mediated mRNA Delivery Reduces Pancreatic Tumors.
    Taylor E Escher, Simseok A Yuk, Yuan Qian, Wenan Qiang, Sultan Almunif, Swagat Sharma, Evan A Scott, Karla J F Satchell.
      Therapeutic gene expression can address many of the challenges associated with the controlled delivery of intracellularly active biologics, such as enzymes that degrade RAS for the treatment of RAS-driven cancers. Here, we demonstrate that an optimized synthetic nonviral gene delivery platform composed of poly(ethylene glycol)-b-poly(propylene sulfide) (PEG-PPS) can block copolymers conjugated to a dendritic cationic peptide (PPDP2) for nontoxic delivery and therapeutic expression of mRNA within human pancreatic cancer cells and tumors. The naturally occurring bacterial enzyme RAS/RAP1-specific endopeptidase (RRSP) is a potent RAS degrader that specifically targets all RAS isoforms. Using PPDP2, rrsp-mRNA is delivered to human pancreatic cells, resulting in RRSP protein expression, degradation of RAS, and loss of cell proliferation. Further, pancreatic tumors are reduced with residual tumors lacking detectable RAS and phosphorylated ERK. Using structural modeling, we further demonstrate that a noncatalytic RAS-binding domain of RRSP provides high specificity for RAS. These data support the notion that the synthetic nanocarrier PPDP2 can deliver rrsp-mRNA to pancreatic tumor cells to interrupt the RAS signaling system.
    Keywords:  RAS; RRSP; degrader; mRNA; nanoparticle; protease; synthetic nanocarrier
    DOI:  https://doi.org/10.1021/acsabm.5c00179
  34. Nature. 2025 May 28.
    Protein-primed homopolymer synthesis by an antiviral reverse transcriptase.
    Stephen Tang, Rimantė Žedaveinytė, Nathaniel Burman, Shishir Pandey, Josephine L Ramirez, Louie M Kulber, Tanner Wiegand, Royce A Wilkinson, Yanzhe Ma, Dennis J Zhang, George D Lampe, Mirela Berisa, Marko Jovanovic, Blake Wiedenheft, Samuel H Sternberg.
      Bacteria defend themselves from viral predation using diverse immune systems, many of which target foreign DNA for degradation1. Defense-associated reverse transcriptase (DRT) systems provide an intriguing counterpoint to this strategy by leveraging DNA synthesis instead2,3. We and others recently showed that DRT2 systems use an RNA template to assemble a de novo gene that encodes an antiviral effector protein, Neo4,5. It remains unknown whether similar mechanisms of defense are employed by other related DRT families. Focusing on DRT9, here we uncover an unprecedented mechanism of DNA homopolymer synthesis. Viral infection triggers polydeoxyadenylate (poly-dA) accumulation in the cell, driving abortive infection and population-level immunity. Cryo-EM structures reveal how a noncoding RNA serves as both a structural scaffold and reverse transcription template to direct hexameric complex assembly and poly-dA synthesis. Remarkably, biochemical and functional experiments identify tyrosine residues within the reverse transcriptase itself that likely prime DNA synthesis, leading to the formation of high-molecular weight protein-DNA covalent adducts. Synthesis of poly-dA by DRT9 in vivo is regulated by the competing activities of phage-encoded triggers and host-encoded silencers. Collectively, our work unveils a novel nucleic acid-driven defense system that expands the paradigm of bacterial immunity and broadens the known functions of reverse transcriptases.
    DOI:  https://doi.org/10.1038/s41586-025-09179-5
  35. ACS Nano. 2025 May 25.
    Unraveling the Impact of Competing Interactions on Nonequilibrium Colloidal Gelation.
    Joeri Opdam, Michio Tateno, Hajime Tanaka.
      Competing interactions stabilize exotic mesoscopic structures, yet the microscopic mechanisms by which they influence nonequilibrium processes leading to disordered states remain largely unexplored, despite their critical role in self-assembly across a range of nanomaterials and biological systems. Here, we numerically investigate the structural evolution in charged colloidal model systems, where short-range attractions and long-range repulsions compete. We reveal that these two interaction scales drive sequential ordering within clusters, from tetrahedra motifs to linear aggregates with chiral order. This process disrupts early stage percolated networks, resulting in reentrant behavior─a dynamic transition from disordered clusters to network to chiral rigid clusters. On the other hand, the cluster-elastic network boundary in the final state is governed by isostatic percolation, which slows structural rearrangements, preserves branching points, and sustains a long-lived network. The resulting structure consists of rigid Bernal spiral-like branches connected through flexible branching points lacking order. These insights advance our microscopic understanding of out-of-equilibrium ordering driven by competing interactions, especially phenomena such as temporally delayed frustration reflecting different length scales of competing interactions. The mechanisms identified here may play a crucial role in mesoscale self-organization across soft materials, from nanoparticle assemblies to biological gels and cytoskeletal networks. Understanding how competing interactions regulate structure and dynamics could guide the design of adaptive materials with tunable mechanical properties and offer valuable insights into biological processes such as cytoplasmic organization and cellular scaffolding.
    Keywords:  Bernal spiral; Colloids; Competing interactions; Depercolation; Gelation; Microscopic structure
    DOI:  https://doi.org/10.1021/acsnano.5c03244
  36. Nat Commun. 2025 May 26. 16(1): 4878
    Spatiotemporal development of expanding bacterial colonies driven by emergent mechanical constraints and nutrient gradients.
    Harish Kannan, Hui Sun, Mya Warren, Tolga Çağlar, Pantong Yao, Brian R Taylor, Kinshuk Sahu, Daotong Ge, Matteo Mori, David Kleinfeld, JiaJia Dong, Bo Li, Terence Hwa.
      Bacterial colonies growing on solid surfaces can exhibit robust expansion kinetics, with constant radial growth and saturating vertical expansion, suggesting a common developmental program. Here, we study this process for Escherichia coli cells using a combination of modeling and experiments. We show that linear radial colony expansion is set by the verticalization of interior cells due to mechanical constraints rather than radial nutrient gradients as commonly assumed. In contrast, vertical expansion slows down from an initial linear regime even while radial expansion continues linearly. This vertical slowdown is due to limitation of cell growth caused by vertical nutrient gradients, exacerbated by concurrent oxygen depletion. Starvation in the colony interior results in a distinct death zone which sets in as vertical expansion slows down, with the death zone increasing in size along with the expanding colony. Thus, our study reveals complex heterogeneity within simple monoclonal bacterial colonies, especially along the vertical dimension. The intricate dynamics of such emergent behavior can be understood quantitatively from an interplay of mechanical constraints and nutrient gradients arising from obligatory metabolic processes.
    DOI:  https://doi.org/10.1038/s41467-025-60004-z
  37. Nat Commun. 2025 May 24. 16(1): 4839
    Designing pathways for bioproducing complex chemicals by combining tools for pathway extraction and ranking.
    Anastasia Sveshnikova, Omid Oftadeh, Vassily Hatzimanikatis.
      The synthesis of many important biochemicals involves complex molecules and numerous reactions. The design and optimization of whole-cell biocatalysts for the production of these molecules requires metabolic modeling to extract production pathways from biochemical databases and integrate them into genome-scale models of the host. However, the synthesis of such complex molecules often requires reactions from multiple pathways operating in balanced subnetworks that are not assembled in existing databases. Here, we present SubNetX, a computational algorithm that extracts reactions from a database and assembles balanced subnetworks to produce a target biochemical from selected precursor metabolites, energy currencies, and cofactors. These subnetworks can be integrated into whole-cell models, allowing the reconstruction and ranking of alternative biosynthetic pathways based on yield, length, and other design goals. We apply SubNetX to 70 industrially relevant natural and synthetic chemicals to demonstrate the application of this pipeline.
    DOI:  https://doi.org/10.1038/s41467-025-59827-7
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