bims-enlima Biomed News
on Engineered living materials
Issue of 2025–06–29
53 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool
  1. Reinforcement of Fibrillar Collagen Hydrogels with Bioorthogonal Covalent Crosslinks.
  2. A biocompatible Lossen rearrangement in Escherichia coli.
  3. Microstructured thermo-responsive double network granular hydrogels.
  4. Rational design matrix materials for organoid development and application in biomedicine.
  5. Engineered Marine Biofilms for Ocean Environment Monitoring.
  6. Reversible Control of Rheological Properties in Microgel Composites via Nanoparticle Aggregation.
  7. A bioinspired and degradable riboflavin-containing polypeptide as a sustainable material for energy storage.
  8. Reversible Phase Transitions of Anionic and Cationic Surfactant Mixtures Drive Shape Morphing Droplets.
  9. Gradient refractive indices enable squid structural color and inspire multispectral materials.
  10. Controlling diverse robots by inferring Jacobian fields with deep networks.
  11. Nonequilibrium polysome dynamics promote chromosome segregation and its coupling to cell growth in Escherichia coli.
  12. Chitin-Core Chitosan-Sheath Nanowhiskers as a Multifunctional Bionanofiber Modality for Hydrogel Microspheres in a Micromolding-Based Fabrication-Conjugation Approach.
  13. A Multilayered Biocontainment System for Laboratory and Probiotic Yeast.
  14. Tailoring the adjuvanticity of lipid nanoparticles by PEG lipid ratio and phospholipid modifications.
  15. Deep Eutectic Inks for Multiphoton 3D Laser Microprinting.
  16. Temperature-Responsive Rheology Modifiers from Cellulose to Enable Acoustic Additive Manufacturing of Hydrogels.
  17. Everyday painkiller made from plastic - by E. coli.
  18. Electrically conductive biopolymer-based hydrogels and fibrous materials fabricated using 3D printing and electrospinning for cardiac tissue engineering.
  19. Controlling Assembly of Hybrid DNA Nanostructures into Higher-Order Structures via Hydrophobicity.
  20. Designing pores to suppress crack generation at the interface between serpentine interconnects and elastomers for highly durable stretchable electronics.
  21. Pathway Refactoring for Efficient 7-Dehydrocholesterol Production in Saccharomyces cerevisiae.
  22. Programmable cell aggregation by a synthetic biosilicification approach.
  23. Tuneable Hydrogel Porosity via Dynamic Tailoring of Spinodal Decomposition.
  24. Phototriggered RNase H-Powered Patterning of Caged DNA/RNA-Functionalized Interfaces Using DNA-Modified Particles, Liposomes, and Cells as Rolling Motors.
  25. Mechanobiology in Action: Biomaterials, Devices, and the Cellular Machinery of Force Sensing.
  26. Acid-Adaptive Polymers Capable of Proton-Capturing and Matrix-Strengthening.
  27. CryoDRGN-AI: neural ab initio reconstruction of challenging cryo-EM and cryo-ET datasets.
  28. Confinement Suppresses Mechanical Force-Mediated Cancer Cell Apoptosis.
  29. The cellular substrate of evolutionary novelty.
  30. Regulation of bacterial phosphorelay systems.
  31. Outside influences: The impact of extracellular matrix mechanics on cell migration.
  32. Elucidating Mechanisms of Gelation, Fiber Assembly, and Stability of Injectable Decellularized Extracellular Matrix Biomaterials.
  33. Autonomous chemo-metabolic construction of anisotropic cell-in-shell nanobiohybrids in enzyme-powered cell microrobots.
  34. High-performance yet sustainable epoxy composites: from Diels-Alder chemistry to hydrazinolytic degradation.
  35. Challenges of alignment in synthetic cell research.
  36. How and when organisms edit their own genomes.
  37. UV-Resistant Cell-Free Reactions with Synthetic Melanin Additives.
  38. Interplay of actin nematodynamics and anisotropic tension controls endothelial mechanics.
  39. Cytoplasmic anillin and Ect2 promote RhoA/myosin II-dependent confined migration and invasion.
  40. Immunization with peptide encapsulated within synthetic spores activates T cell responses and reduces tumor growth.
  41. Microbial Dynamic Regulatory Tools: Design, Applications, and Prospects.
  42. Tuning Biomaterial Surfaces to Modulate Host-Immune Reactions.
  43. Scalable production of human cortical organoids using a biocompatible polymer.
  44. Structure of lymphostatin, a large multi-functional virulence factor of pathogenic Escherichia coli.
  45. A class of benzofuranoindoline-bearing heptacyclic fungal RiPPs with anticancer activities.
  46. Mammalian fatty acid synthase: a commonly used viral host dependency factor and a putative target for host-targeted broad-spectrum antiviral therapeutic development.
  47. Kinetic-model-guided engineering of multiple S. cerevisiae strains improves p-coumaric acid production.
  48. Sequestration of ribosome biogenesis factors in HSV-1 nuclear aggregates revealed by spatially resolved thermal profiling.
  49. Development of Polysaccharide Hydrogels Enriched With Protein and Starch for Bovine Myoblast Cell Culture.
  50. Bioprinting of GelMA-Based Hydrogels to Aid in Creation of Biomimetic 3D Models for Glioblastoma.
  51. Programmable DNA-Based Molecular Neural Network Biocomputing Circuits for Solving Partial Differential Equations.
  52. Improving engineered biological systems with electronics and microfluidics.
  53. Post-Transcriptional Modifications of the Large Ribosome Subunit Assembly Intermediates in E. coli Expressing a Helicase-Inactive DbpA Variant.
  1. Biomacromolecules. 2025 Jun 24.
    Reinforcement of Fibrillar Collagen Hydrogels with Bioorthogonal Covalent Crosslinks.
    Lucia G Brunel, Chris M Long, Fotis Christakopoulos, Betty Cai, Narelli de Paiva Narciso, Patrik K Johansson, Diya Singhal, Neil J Baugh, Daiyao Zhang, Annika Enejder, David Myung, Sarah C Heilshorn.
      Bioorthogonal covalent crosslinking stabilizes collagen type I hydrogels, improving their structural integrity for tissue engineering applications with encapsulated living cells. The chemical modification required for crosslinking, however, interferes with the fibrillar nature of the collagen, leading instead to an amorphous network without fibers. We demonstrate an approach to perform bioconjugation chemistry on collagen with controlled localization such that the modified collagen retains its ability to self-assemble into a fibrillar network while also displaying functional groups for covalent crosslinking with bioorthogonal click chemistry. The collagen matrix is formed through a sequential crosslinking process, in which the modified collagen first physically assembles into fibers and then is covalently crosslinked. This approach preserves the fibrous architecture of the collagen, guiding the behavior of encapsulated human corneal mesenchymal stromal cells while also reinforcing fibers through covalent crosslinks, strengthening the stability of the cell-laden collagen hydrogel against cell-induced contraction and enzymatic degradation.
    DOI:  https://doi.org/10.1021/acs.biomac.5c00398
  2. Nat Chem. 2025 Jun 23.
    A biocompatible Lossen rearrangement in Escherichia coli.
    Nick W Johnson, Marcos Valenzuela-Ortega, Thomas W Thorpe, Yuta Era, Annemette Kjeldsen, Keith Mulholland, Stephen Wallace.
      Nature has evolved an exquisite yet limited set of chemical reactions that underpin the function of all living organisms. By contrast, the field of synthetic organic chemistry can access reactivity not observed in nature, and integration of these abiotic reactions within living systems offers an elegant solution to the sustainable synthesis of many industrial chemicals from renewable feedstocks. Here we report a biocompatible Lossen rearrangement that is catalysed by phosphate in the bacterium Escherichia coli for the transformation of activated acyl hydroxamates to primary amine-containing metabolites in living cells. Through auxotroph rescue, we demonstrate how this new-to-nature reaction can be used to control microbial growth and chemistry by generating the essential metabolite para-aminobenzoic acid. The Lossen rearrangement substrate can also be synthesized from polyethylene terephthalate and applied to whole-cell biocatalytic reactions and fermentations generating industrial small molecules (including the drug paracetamol), paving the way for a general strategy to bioremediate and upcycle plastic waste in native and engineered biological systems.
    DOI:  https://doi.org/10.1038/s41557-025-01845-5
  3. Mater Adv. 2025 Jun 16.
    Microstructured thermo-responsive double network granular hydrogels.
    Alexandra Thoma, Reece Whatmore, Esther Amstad.
      Many hydrogels respond to external stimuli such as changes in temperature, pH, or salt concentrations by changing their degree of swelling, and hence mechanical properties, rendering them attractive actuators. Unfortunately, response rates of many of these hydrogels are limited because they rely on the diffusion of water, which is relatively slow within the gel. Here, we introduce thermo-responsive granular hydrogels which combine accelerated response rates with load-bearing properties. To accelerate the response to temperature changes, we formulate poly(N-isopropylacrylamide) (PNIPAM) microgels with connected pores by leveraging phase separations. To impart the porous hydrogel load-bearing properties, we formulate them as thermo-responsive double network granular hydrogels (TDNGHs). We demonstrate that the granular structure combined with the open micropores located within the microfragments increase the response-rate of these gels 3-fold compared to that of bulk counterparts. Moreover, the granular material exhibits 18-fold enhanced work of fracture compared to the bulk. The granular structure adds an additional benefit: it renders them 3D printable. We co-process thermo-responsive hydrogels with a non-responsive counterpart to fabricate a bilayer, which lifts up to 85% of its weight if heated and 3D print a butterfly as a bilayer structure that bends its wings when exposed to elevated temperatures.
    DOI:  https://doi.org/10.1039/d5ma00511f
  4. Regen Biomater. 2025 ;12 rbaf038
    Rational design matrix materials for organoid development and application in biomedicine.
    Yue Huang, Xiaoyu Zhang, Wanjun Zhang, Jinglong Tang, Jing Liu.
      Organoids are three-dimensional tissue analogues grown in vitro. Although they are not human organs in the strict sense, they can mimic the structure and function of tissues in vivo to the maximum extent, and have broad application prospects in the fields of organ development, personalized medicine, regenerative medicine, disease modeling, drug screening, gene editing, etc. There is even hope that organoids can replace experimental animals for preclinical testing, which will greatly shorten the cycle of preclinical testing and improve its efficiency. Nowadays, Matrigel remains the predominant substitute for organoid culture systems. At the same time, new extracellular matrix or inspired polymer materials with tunable and optimized biochemical and biophysical properties continue to emerge, which are of great significance for efficient and high-level cultivation of organoids. In this review, we critically evaluate how mechanobiological signaling dynamics at the cell-matrix interface inform the rational engineering of biomimetic extracellular matrices to achieve standardized and phenotypically regulated patient-derived organoid cultures. Then, we systematically classify hydrogel-based matrices encompassing natural, biohybrid, synthetic, protein-engineered and DNA crosslinked matrix systems by their biocompatibility and functional compatibility. Focusing on cancer oncogenesis and progression research, drug development and personalized medicine, we highlight biomimetic hydrogel innovations that recapitulate tumor organoids development. By summarizing the obstacles that hinder the development of organoid hydrogels, we hope to provide an outlook on the future directions for the development of organoid hydrogels and promote the application of organoids in the field of biomedicine.
    Keywords:  biomedicine; cancer; drug-screening; hydrogels; organoid
    DOI:  https://doi.org/10.1093/rb/rbaf038
  5. ACS Synth Biol. 2025 Jun 22.
    Engineered Marine Biofilms for Ocean Environment Monitoring.
    Guillermo Nevot, Maria Pol Cros, Lorena Toloza, Nil Campamà-Sanz, Maria Artigues-Lleixà, Laura Aguilera, Marc Güell.
      Marine bacteria offer a promising alternative for developing Engineered Living Materials (ELMs) tailored to marine applications. We engineered Dinoroseobacter shibae to increase its surface-associated growth and develop biosensors for ocean environment monitoring. By fusing the endogenous extracellular matrix amyloidogenic protein CsgA with mussel foot proteins, we significantly increased D. shibae biofilm formation. Additionally, D. shibae was engineered to express the tyrosinase enzyme to further enhance microbial attachment through post-translational modifications of tyrosine residues. By exploiting D. shibae's natural genetic resources, two environmental biosensors were created to detect temperature and oxygen. These biosensors were coupled with a CRISPR-based recording system to store transient gene expression in stable DNA arrays, enabling long-term environmental monitoring. These engineered strains highlight D. shibae's potential in advancing marine microbiome engineering for innovative biofilm applications, including the development of natural, self-renewing biological adhesives, environmental sensors, and "sentinel" cells equipped with CRISPR-recording technology to capture and store environmental signals.
    Keywords:  Dinoroseobacter shibae; ELMs; biofilm; biosensors; marine bacteria; surface colonization
    DOI:  https://doi.org/10.1021/acssynbio.5c00192
  6. ACS Appl Mater Interfaces. 2025 Jun 27.
    Reversible Control of Rheological Properties in Microgel Composites via Nanoparticle Aggregation.
    Yul Hui Shim, Tae Yeon Kong, So Youn Kim.
      Microgels are soft materials with tunable rheological properties, making them useful for applications such as 3D printing, drug delivery, and coatings. However, balancing printability and structural stability remains a key challenge. In this study, to overcome this issue, we investigate nanoparticle aggregation as a reversible physical cross-linking mechanism in silica-Carbopol microgel composites. The surface charge of silica nanoparticles is pH-sensitive, resulting in aggregation at low pH and dispersion at high pH. This aggregation enhances rheological properties by increasing elasticity and yield stress, while dispersion reduces the rheological properties by allowing for easy flow. Using SAXS, NMR, and recovery rheology, we characterize these structural transitions and demonstrate that aggregation kinetics can be accelerated by tuning the nanoparticle size, temperature, and concentrations. This tunable cross-linking mechanism allows precise control over microgel behavior, enabling their use as recyclable direct-ink-writing printing inks. By using pH and temperature control, our approach provides a pathway to create microgel composites with reversible mechanical properties, opening new possibilities for advanced ink formulations and sustainable material applications.
    Keywords:  aggregation; composite recycling; microgel; microstructure; nanoparticle; polymer nanocomposite; rheology
    DOI:  https://doi.org/10.1021/acsami.5c06287
  7. Proc Natl Acad Sci U S A. 2025 Jul;122(26): e2509325122
    A bioinspired and degradable riboflavin-containing polypeptide as a sustainable material for energy storage.
    Shih-Guo Li, Khirabdhi T Mohanty, Alexandra D Easley, Yohannes H Rezenom, Soon-Mi Lim, Leyla P Gillett, Stone D Naquin, David K Tran, Tan P Nguyen, Jodie L Lutkenhaus, Karen L Wooley.
      Inspired by Nature, we present a polypeptide-based organic redox-active material constructed from renewable feedstocks, L-glutamic acid (an amino acid) and riboflavin (vitamin B2), to address challenges with start-to-end-of-life management in energy storage systems (ESSs). The amino acid was utilized to establish a degradable polymer backbone, along which many copies of riboflavin were incorporated to serve as the redox-active pendant groups that enabled energy storage. The overall synthesis involved the ring-opening polymerization (ROP) of an l-glutamic acid-derived N-carboxyanhydride (NCA) monomer, followed by side chain activation with azides and, finally, click coupling to achieve installation of alkyne-functionalized riboflavin moieties. The steric bulkiness and rich chemical functionality of riboflavin resulted in synthetic complexities that required reaction optimization to achieve the desired polymer structure. Electrochemical characterization of the resultant riboflavin polypeptide, in organic electrolyte, showed quasireversible redox activity with a half-wave potential (E1/2) of ca. -1.10 V vs. ferrocene/ferrocenium (Fc/Fc+). Cell viability assays revealed biocompatibility, as indicated by negligible cytotoxicity for fibroblast cells. The polypeptide design, consisting of labile amide backbone linkages and side-chain ester functionalities that tethered the riboflavin units to the backbone, enabled hydrolytic degradation to recover building blocks for future upcycling or recycling. This bioinspired strategy advances the development of degradable redox-active polymers and promotes sustainable materials design for circular energy storage technologies.
    Keywords:  ; bioderived redox-active material; controlled ring-opening polymerization; degradable polymers; sustainable energy storage
    DOI:  https://doi.org/10.1073/pnas.2509325122
  8. Adv Mater. 2025 Jun 26. e2506100
    Reversible Phase Transitions of Anionic and Cationic Surfactant Mixtures Drive Shape Morphing Droplets.
    Bradley D Frank, Pilar Romero, Alberto Concellón, Lukas Zeininger.
      Converting chemical signals into mechanical responses is fundamental to biological systems, driving processes such as cellular motility and tissue morphogenesis. Yet, harnessing chemo-mechanical signal conversions in synthetic systems remains a key challenge in energy-dissipative materials design. While droplets can move and interact with their environment reminiscent of active biological matter, chemo-mechanical interactions are limited by the translation of chemical changes into extensive force variations required on small timescales. Droplets naturally adopt spherical shapes to minimize surface-energy and restructuring liquids into non-equilibrium geometries requires mechanisms beyond current stimuli-responsive surfactant systems, which lack the force-amplifying mechanisms needed for transient liquid structuring. Here, a spring-like charging and latch-controlled release mechanism is introduced for actuating droplets. This is based on reversible, light-induced crystal-to-coacervate phase transitions of photo-responsive surfactant assemblies, namely between anionic sodium dodecylsulfate and cationic azobenzene-based surfactants. During phase-transition, reversible partitioning of the surfactants into the oil or aqueous phases of the emulsion transiently induce rapid changes in interfacial tensions, which are up to 900 times greater than those observed for conventional stimuli-responsive surfactant systems. The insights into this novel chemo-mechanical transduction mechanism provide new control over purely liquid systems, paving the way for programmable, hierarchically structured, all-liquid matter acting with physicality.
    Keywords:  active matter; droplets; liquid crystals; out‐of‐equilibrium; soft robotics; stimuli‐responsive surfactants
    DOI:  https://doi.org/10.1002/adma.202506100
  9. Science. 2025 Jun 26. 388(6754): 1389-1395
    Gradient refractive indices enable squid structural color and inspire multispectral materials.
    Georgii Bogdanov, Aleksandra Anna Strzelecka, Nikhil Kaimal, Stephen L Senft, Sanghoon Lee, Roger T Hanlon, Alon A Gorodetsky.
      The manipulation of light by means of materials with varying refractive index distributions is widespread among natural systems and modern technologies. However, understanding how animals leverage refractive index differences for dynamic color changes and then translating such insight into tunable optical devices remains challenging. We experimentally and computationally demonstrated that iridescent cells (iridophores) containing Bragg reflectors with sinusoidal-wave (rugate) refractive index profiles enable squid dorsal mantle tissues to reversibly transition between nearly transparent and vibrantly colored states. We then drew inspiration from these findings for the design and development of iridophore-inspired multispectral composite materials with tunable visible and infrared functionalities. Our study provides insight into squid dynamic structural coloration mechanisms and furnishes a technology for camouflage, heat management, display, and sensing applications.
    DOI:  https://doi.org/10.1126/science.adn1570
  10. Nature. 2025 Jun 25.
    Controlling diverse robots by inferring Jacobian fields with deep networks.
    Sizhe Lester Li, Annan Zhang, Boyuan Chen, Hanna Matusik, Chao Liu, Daniela Rus, Vincent Sitzmann.
      Mirroring the complex structures and diverse functions of natural organisms is a long-standing challenge in robotics1-4. Modern fabrication techniques have greatly expanded the feasible hardware5-8, but using these systems requires control software to translate the desired motions into actuator commands. Conventional robots can easily be modelled as rigid links connected by joints, but it remains an open challenge to model and control biologically inspired robots that are often soft or made of several materials, lack sensing capabilities and may change their material properties with use9-12. Here, we introduce a method that uses deep neural networks to map a video stream of a robot to its visuomotor Jacobian field (the sensitivity of all 3D points to the robot's actuators). Our method enables the control of robots from only a single camera, makes no assumptions about the robots' materials, actuation or sensing, and is trained without expert intervention by observing the execution of random commands. We demonstrate our method on a diverse set of robot manipulators that vary in actuation, materials, fabrication and cost. Our approach achieves accurate closed-loop control and recovers the causal dynamic structure of each robot. Because it enables robot control using a generic camera as the only sensor, we anticipate that our work will broaden the design space of robotic systems and serve as a starting point for lowering the barrier to robotic automation.
    DOI:  https://doi.org/10.1038/s41586-025-09170-0
  11. Elife. 2025 Jun 24. pii: RP104276. [Epub ahead of print]14
    Nonequilibrium polysome dynamics promote chromosome segregation and its coupling to cell growth in Escherichia coli.
    Alexandros Papagiannakis, Qiwei Yu, Sander K Govers, Wei-Hsiang Lin, Ned S Wingreen, Christine Jacobs-Wagner.
      Chromosome segregation is essential for cellular proliferation. Unlike eukaryotes, bacteria lack cytoskeleton-based machinery to segregate their chromosomal DNA (nucleoid). The bacterial ParABS system segregates the duplicated chromosomal regions near the origin of replication. However, this function does not explain how bacterial cells partition the rest (bulk) of the chromosomal material. Furthermore, some bacteria, including Escherichia coli, lack a ParABS system. Yet, E. coli faithfully segregates nucleoids across various growth rates. Here, we provide theoretical and experimental evidence that polysome production during chromosomal gene expression helps compact, split, segregate, and position nucleoids in E. coli through nonequilibrium dynamics that depend on polysome synthesis, degradation (through mRNA decay), and exclusion from the DNA meshwork. These dynamics inherently couple chromosome segregation to biomass growth across nutritional conditions. Halting chromosomal gene expression and thus polysome production immediately stops sister nucleoid migration, while ensuing polysome depletion gradually reverses nucleoid segregation. Redirecting gene expression away from the chromosome and toward plasmids causes ectopic polysome accumulations that are sufficient to drive aberrant nucleoid dynamics. Cell width enlargement experiments suggest that limiting the exchange of polysomes across DNA-free regions ensures nucleoid segregation along the cell length. Our findings suggest a self-organizing mechanism for coupling nucleoid compaction and segregation to cell growth without the apparent requirement of regulatory molecules.
    Keywords:  E. coli; cell biology; cytoplasmic heterogeneity; non-equilibrium processes; nucleoid segregation; phase separation; polysome dynamics; single-cell microscopy
    DOI:  https://doi.org/10.7554/eLife.104276
  12. ACS Appl Bio Mater. 2025 Jun 27.
    Chitin-Core Chitosan-Sheath Nanowhiskers as a Multifunctional Bionanofiber Modality for Hydrogel Microspheres in a Micromolding-Based Fabrication-Conjugation Approach.
    Alec K Zackin, Subhash Kalidindi, Hyunmin Yi.
      Simple and tunable production of macroporous hydrogel microparticles for rapid protein quantification in a suspension array format remains a major challenge. We exploit biologically derived rigid nanofibers as a multifunctional modality in a robust micromolding method using a postfabrication bioconjugation approach to address this challenge. Specifically, chitin-core chitosan-sheath nanowhiskers (CSNW) with a tunable amine titer are prepared under mild deacetylation reaction conditions. Transmission electron microscopy, dynamic light scattering, and dynamic viscosity measurements show rigid bionanofibers with substantially lower viscosity compared to solubilized linear forms of chitosan and other biopolymers, suggesting improved handling and manufacturability. Fluorescent labeling studies on polyacrylamide-based microspheres fabricated via micromolding indicate stable and uniform incorporation of CSNW in hydrogel microspheres and the readily tunable chemical functionality of CSNW. Further, reliable fabrication using acrylate-modified CSNW as the primary cross-linker, along with selective and improved protein conjugation kinetics, attests to the macroporous network of the hydrogel microparticles and illustrates the multifunctionality of CSNW. We thus envision that our approach in harnessing potent bionanofibers and micromolding can be readily extended to produce a wide variety of multifaceted microscale materials with a multitude of desirable features with improved performances for applications such as rapid biosensing and biodiagnostics.
    Keywords:  Bioconjugation; Hydrogels; Micromolding; Microparticles; chitin-core chitosan-sheath nanowhisker
    DOI:  https://doi.org/10.1021/acsabm.5c00632
  13. Metab Eng. 2025 Jun 25. pii: S1096-7176(25)00095-3. [Epub ahead of print]
    A Multilayered Biocontainment System for Laboratory and Probiotic Yeast.
    Carla Maneira, Sina Becker, Alexandre Chamas, Gerald Lackner.
      The containment of genetically engineered microorganisms to designated environments of action is a paramount step in preventing their spread to nature. Physical barriers were traditionally employed to solve this issue, nevertheless, the growing number of biotechnological operations in open dynamic environments calls for intrinsic biocontainment. Here we describe the development of genetically embedded safeguard systems for both a laboratory strain of Saccharomyces cerevisiae and the commercial probiotic Saccharomyces cerevisiae var. boulardii. In a stepwise approach, single-input metabolic circuits based either on a synthetic auxotrophy or a CRISPR-based kill switch were developed before their combination into an orthogonal two-input system. All circuits are based on gut-active molecules or environmental cues, making them amenable to microbiome therapy applications. The final two-input system is stable for more than a hundred generations while achieving less than one escapee in 109 CFUs after incubation under restrictive conditions for at least six days. Biocontained strains can robustly produce heterologous proteins under permissive conditions, supporting their future use in the most varied applications, like in-situ production and delivery of pharmaceutically active metabolites.
    Keywords:  Biocontainment; Engineered live biotherapeutic products; Saccharomyces boulardii; Saccharomyces cerevisiae; Synthetic biology
    DOI:  https://doi.org/10.1016/j.ymben.2025.06.009
  14. Nat Nanotechnol. 2025 Jun 23.
    Tailoring the adjuvanticity of lipid nanoparticles by PEG lipid ratio and phospholipid modifications.
    Máté Vadovics, Wenchen Zhao, Emily F Daley, Kieu Lam, Owen Daly, Khalid Rashid, Hailey R Lee, Petra Schreiner, Kendall A Lundgreen, Brian T Gaudette, Vladimir V Shuvaev, Evguenia Arguiri, Hiromi Muramatsu, András Sárközy, Thandiswa Mdluli, Junchao Xu, Xuexiang Han, Nina De Luna, Diana Castaño, Emily Bettini, Edit Ábrahám, Zoltan Lipinszki, Giuseppe Carlucci, Avinash Haridas Bansode, Katelyn Nguyen, Thuc M Le, Tony Luu, Vladimir R Muzykantov, Paul Bates, David Allman, Michael J Mitchell, Michela Locci, Caius G Radu, James Heyes, Norbert Pardi.
      Lipid nanoparticles (LNPs) represent the leading delivery platform for mRNA vaccines with advantageous biocompatibility, scalability, adjuvant activity and often an acceptable safety profile. Here we investigate the physicochemical characteristics and adjuvanticity of four-component LNPs. Previous vaccine studies have demonstrated that altering the ionizable lipid influences the adjuvanticity of an LNP; however, the impact of the polyethylene glycol lipid and phospholipid has received less attention. Our mRNA-LNP vaccine formulations utilized different phospholipids and varying ratios of polyethylene glycol lipid, whereas the ionizable lipid and cholesterol remained approximately constant. We demonstrate that such modifications impact the magnitude and quality of the vaccine-elicited immune responses. We also dissect the underlying mechanisms and show that the biodistribution and cellular uptake of LNPs correlate with the magnitude and quality of the immune responses. These findings support the rational design of novel LNPs to tailor immune responses (cellular or humoral focused) based on the vaccine application.
    DOI:  https://doi.org/10.1038/s41565-025-01958-5
  15. Adv Mater. 2025 Jun 25. e2507640
    Deep Eutectic Inks for Multiphoton 3D Laser Microprinting.
    Philipp Mainik, Christoph A Spiegel, Jonathan L G Schneider, Martin Wegener, Eva Blasco.
      Multiphoton 3D laser printing of polymers has become a widespread technology for manufacturing 3D architectures on the micro- and nanometer scale, with booming applications in micro-optics, micro-robotics, and micro-scaffolds for biological cell culture. However, many applications demand material properties that are not accessible by conventional polymer inks. These include large stiffness, for which recent breakthroughs based on inorganic materials have been reported. Conversely, some applications require very low stiffness and high mechanical compliance. Existing solutions achieve softness by low crosslinking densities, at the inherent expense of deteriorated spatial resolution and structure quality. Herein, this apparent contradiction is resolved by introducing multiphoton inks based on deep eutectic systems, comprising Lewis or Brønsted acids/bases. The 3D printed materials support extremely large strains and bulk Young's moduli as low as 260 kPa under aqueous conditions, well suited for biological applications - at comparable ease of use and spatial resolution as well-established commercially available polymer inks.
    Keywords:  4D printing; light‐based 3D printing; polymerizable deep eutectic solvents; soft materials; stimuli‐responsive polymers
    DOI:  https://doi.org/10.1002/adma.202507640
  16. ACS Macro Lett. 2025 Jun 27. 976-982
    Temperature-Responsive Rheology Modifiers from Cellulose to Enable Acoustic Additive Manufacturing of Hydrogels.
    Lillian E Mortensen, Fernando Enriquez Barrero, Talaial B Alina, Jennifer N Cha, Andrew P Goodwin.
      While photopolymerization is a widely adopted method for additive manufacturing, its versatility is limited by high attenuation by the polymerization medium, which leads to anisotropic parts and slow printing times. Ultrasound bypasses these depth limitations, but challenges of acoustic streaming and heat localization remain. Here, we investigated a single-phase system that integrates temperature-responsive rheology modifiers to enhance ultrasound-based additive manufacturing. We employed cellulose derivatives with lower critical solution temperatures (LCST) to restrict acoustic streaming and localize heat within the focal zone. Our findings show that these rheology modifiers effectively contain heat, minimizing bulk polymerization and enhancing printing precision. Hydroxypropyl cellulose (HPC)-based sono-inks enable rapid printing speeds of up to 60 mm/min with sub-5 mm resolution. Furthermore, HPC inks demonstrated the capability to print at a distance and through optically opaque tissues. Conversely, methylcellulose (MC) formulations improved printing resolution but reduced speed, likely because the LCST could not be reached during the printing process. The developed sono-ink holds promise for future applications such as in vivo 3D printing, volumetric fabrication, and composite material synthesis.
    DOI:  https://doi.org/10.1021/acsmacrolett.5c00244
  17. Nature. 2025 Jun 26.
    Everyday painkiller made from plastic - by E. coli.
    Rita Aksenfeld.
      
    Keywords:  Biochemistry; Chemistry; Drug discovery
    DOI:  https://doi.org/10.1038/d41586-025-01986-0
  18. Bioact Mater. 2025 Sep;51 650-719
    Electrically conductive biopolymer-based hydrogels and fibrous materials fabricated using 3D printing and electrospinning for cardiac tissue engineering.
    Arnaud Kamdem Tamo, Ingo Doench, Kaveh Roshanbinfar, Alexandra Montembault, Anatoli Serghei, Felix B Engel, Anayancy Osorio-Madrazo.
      Cardiovascular diseases pose a significant global health challenge, driving ongoing efforts to develop effective treatments. Various biofabrication technologies utilizing numerous materials have been employed to design functional cardiac tissues. Choosing the right material is crucial to support cardiac cell growth, proliferation, tissue maturation and functionality. 3D printing enables the fabrication of structures that mimic the hierarchical organization of native cardiac tissue, further enhancing its function. Electrospinning produces nanofibrous scaffolds with a high surface area and porosity, mimicking the extracellular matrix and promoting the cell behaviors required for tissue formation. Although typically employed independently, combining these technologies can enable the fabrication of patches with properties closely resembling those of native cardiac tissues. Recent research focuses on the use of electroconductive materials, which enhance cell-to-cell communication and promote the maturation of cardiomyocytes, thereby preventing arrhythmic contractions and improving the functionality of engineered cardiac tissues. In this review, recent studies showcasing the applications of electroconductive biopolymer-based fibrous materials and hydrogels designed using 3D printing and/or electrospinning for cardiac tissue engineering are discussed. Furthermore, the review evaluates the synergistic effects of biopolymer-based materials and electrical components in 3D printed electroconductive hydrogels. It also discusses the challenges faced in fabricating these hydrogels and explores their future prospects for biomedical applications.
    Keywords:  3D (bio)printing; Biopolymer-based hydrogels; Cardiac tissue engineering; Electroconductive hydrogels; Electroconductive materials; Electrospinning; Fiber-filled hydrogels
    DOI:  https://doi.org/10.1016/j.bioactmat.2025.05.014
  19. Angew Chem Int Ed Engl. 2025 Jun 24. e202507844
    Controlling Assembly of Hybrid DNA Nanostructures into Higher-Order Structures via Hydrophobicity.
    Minu Saji, Devanathan Perumal, Qi Yang, Frieder Jaekle, Fei Zhang.
      Hydrophobic interactions are one of the fundamental driving forces of self-assembly in living systems. It remains challenging to harness hydrophobicity to have a controllable and programmable assembly of DNA nanostructures. On the other hand, there is also a need to explore orthogonal hierarchical assembly strategies to be used as an additional toolset along with the traditional Watson-Crick base pairing to achieve complex superstructures. In this work, we rationally design and synthesize a series of low molecular weight hydrophobic molecules that are conjugated to single-stranded DNA strands. By incorporating these modified DNA strands into the precisely defined locations of DNA tiles and origami nanostructures, we achieve controlled hierarchical assembly driven by hydrophobic interaction. We demonstrate a versatile hydrophobicity-guided higher-order assembly strategy by employing strategically engineered DNA nanostructures of increasing complexity, ranging from simple DNA tiles to complex origami structures, functionalized with these small hydrophobic molecules as programmable building blocks.
    Keywords:  DNA structures; Hybrid Materials; Hydrophobic Effect; Self-assembly
    DOI:  https://doi.org/10.1002/anie.202507844
  20. Mater Horiz. 2025 Jun 23.
    Designing pores to suppress crack generation at the interface between serpentine interconnects and elastomers for highly durable stretchable electronics.
    Seungkyu Lee, Jun Chang Yang, Steve Park.
      Serpentine interconnects enable rigid materials to have high stretchability. They are considered to be very effective architectures to enable stretchable electronics. Therefore, research has primarily focused on exploring serpentine-based designs to enhance the stretchability of the interconnect itself. However, in practical applications, the interfacial cracks caused by repetitive stretching becomes a critical issue if serpentine interconnects are encapsulated within a polymer matrix. Here, we introduce geometrically engineered pores in a polymer matrix to suppress interfacial cracks under stretching. The serpentine interconnects with optimized pores in a polymer matrix improved mechanical stability (strain at failure, fatigue life) and electrical stability compared with those without pores. Furthermore, these strategies enabled the demonstration of a stretchable light-emitting diodes (LED) array and an electrical heater.
    DOI:  https://doi.org/10.1039/d5mh00555h
  21. ACS Synth Biol. 2025 Jun 27.
    Pathway Refactoring for Efficient 7-Dehydrocholesterol Production in Saccharomyces cerevisiae.
    Yuchen Han, Huayi Gao, Shuo Wang, Haiyan Ju, Ran Ge, Chaoyou Xue, Weidong Liu, Xiaolong Jiang, Wuyuan Zhang.
      7-Dehydrocholesterol (7-DHC) is a subcutaneous sterol and a precursor to various active vitamin D3. Here, a Saccharomyces cerevisiae strain equipped with the de novo biosynthetic pathway for 7-DHC was constructed. 109.0 mg L-1 of 7-DHC was achieved initially by introducing heterologous 24-dehydrocholesterol reductase (DHCR24) and overexpressing vital enzymes. Following these modifications, the dynamic regulation of the ergosterol pathway and multicopy expression of DHCR24 resulted in an 86.3% increase in the 7-DHC titer. Subsequently, the effects of several organic solvents and surfactants on 7-DHC production were also explored. The addition of ε-polylysine increased the titer of 7-DHC by 99.1%. Finally, by assembling the pathway in peroxisomes and rebalancing the redox levels, the 7-DHC titer reached 517.4 mg L-1 in shake flasks. Scale-up fermentation with a 5 L bioreactor demonstrated that 3.26 g L-1 of 7-DHC was produced. The pathway refactoring strategy provides efficient production of 7-DHC in a sustainable manner.
    Keywords:  7-dehydrocholesterol; Saccharomyces cerevisiae; biosynthesis; cell factory; membrane structure; peroxisomal targeting
    DOI:  https://doi.org/10.1021/acssynbio.5c00032
  22. iScience. 2025 Jun 20. 28(6): 112519
    Programmable cell aggregation by a synthetic biosilicification approach.
    Qing Wang, Jing Sun, Lei Zang, Huaxiong Yao, Lin Wang, Runtao Zhu, Jie Li, Simin Zeng, Hongting Tang, Teng Wang, Ji Liu, Bo Wang, Bo Li, Zhiyuan Liu, Zhuojun Dai.
      Programmable cell aggregation offers valuable insights into the natural development of synthetic multicellular systems and enables precise control over spatial organization and material structuring. Previous efforts have focused on modifying cells with designed organic-based adhesive modules and assembling cells into defined patterns. Here, we present a different approach to guide cell assembly by tuning the organic-inorganic interactions. Our method involves engineering cells to express a silicifying peptide on their surfaces, which promotes silica deposition on the cell walls. This peptide simultaneously binds to the silica synthesized on adjacent cells, triggering cell clustering. The engineered cells exhibit rapid aggregation, with approximately 95% of cells assembling within 15 min. We further show that this capability can facilitate materials assembly and chemical production. Our biosilicification-based approach offers novel insights into natural multicellularity mechanisms and holds potential for applications in biomanufacturing and materials engineering.
    Keywords:  Bioengineering; Biomaterials; Synthetic biology
    DOI:  https://doi.org/10.1016/j.isci.2025.112519
  23. Adv Sci (Weinh). 2025 Jun 26. e04265
    Tuneable Hydrogel Porosity via Dynamic Tailoring of Spinodal Decomposition.
    Michael Halwes, Callum Vidler, Lilith Caballero Aguilar, Farzaneh Taromian, David R Nisbet, Melanie Stamp, Khoon S Lim, Andrea J O'Connor, David J Collins.
      Pores within hydrogel structures play a crucial role in fostering cell growth and tissue development. The creation and control of pore size and interconnectivity can be conveniently achieved with aqueous two-phase emulsions. The decomposition of these emulsions into two separate phases can be controlled by carefully choosing the polymer components and solution conditions. Spinodal decomposition, a mechanism of phase separation, can result in a highly interconnected pore morphology, though controlling this process is difficult in practice, limiting its application for in vitro models. Here, a straightforward method is introduced for dynamically halting the phase separation of a gelatin methacryloyl and poly(vinyl alcohol) (GelMA-PVA) polymer blend in the context of a biofabrication process based on dynamic interface printing (DIP). This is enabled by a novel approach based on the concerted application of acoustic mixing and photocuring to structure the pore size, orientation, and interconnectivity in hydrogels. This approach accordingly enables spatially addressable fabrication of 3D hydrogel architectures, with the potential to enhance the functionality of engineered tissues via tailored microenvironments.
    Keywords:  GelMA; bioprinting; dynamic interface printing; porous hydrogel; spinodal decomposition
    DOI:  https://doi.org/10.1002/advs.202504265
  24. Small. 2025 Jun 26. e2506270
    Phototriggered RNase H-Powered Patterning of Caged DNA/RNA-Functionalized Interfaces Using DNA-Modified Particles, Liposomes, and Cells as Rolling Motors.
    Danlong Chen, Yunlong Qin, Shijun Xu, Fan Xia, Itamar Willner, Fujian Huang.
      Patterning of photoresponsive RNA/DNA monolayer interfaces by DNA-modified rolling motor particles consisting of SiO2 particles, liposomes and cells is described. The DNA/RNA interface is composed of o-nitrobenzyl phosphate caged RNA hairpin/DNA monolayer. Photochemical uncaging of the interfaces (λ = 365 nm) activates the interface toward binding of the DNA-modified particle frameworks, and in the presence of RNase H stimulates the patterning of the interface by the rolling motor particles. While photoactivation of the entire interface leads to random patterning by rolling motors, photolithographic or/and localized laser confocal microscopy of the surface leads to directional patterning of the photoactivated confined interface domains by the DNA-modified rolling motor frameworks. Moreover, dictated DNA-bridged rolling motor particle assemblies lead to dictated linear patterns that are disrupted into random patterning paths by auxiliary triggered separation of the particle dimers. Furthermore, a method to transform cells into rolling motor patterning frameworks by integration of DNA tetrahedra into the cell membrane is introduced.
    Keywords:  DNA switch; monolayer; particle dimer; photolithography; photoresponsive DNA/RNA
    DOI:  https://doi.org/10.1002/smll.202506270
  25. Biomolecules. 2025 Jun 10. pii: 848. [Epub ahead of print]15(6):
    Mechanobiology in Action: Biomaterials, Devices, and the Cellular Machinery of Force Sensing.
    Miriam Lucariello, Maria Luisa Valicenti, Samuele Giannoni, Leonardo Donati, Ilaria Armentano, Francesco Morena, Sabata Martino.
      Mechanical forces are increasingly recognised as fundamental regulators of cellular function, complementing classical biochemical cues to direct development, tissue homeostasis, and disease progression. Cells detect external and internal forces via mechanosensor proteins and adapt their cytoskeletal architecture, leading to changes in cell behaviour. Biomaterials and biodevices come to the aid of tailoring biomaterials' properties in terms of chemical/physical properties and, by emulating dynamical forces, e.g., shear stress and cell swelling, they may enlighten mechanobiological processes. Additionally, emerging technologies expand the experimental toolkit for probing mechanobiological phenomena in complex, customisable settings. Central to these processes are mechanotransducer proteins and membrane-organelle networks that convert mechanical deformation into biochemical signals, orchestrating downstream transcriptional and post-translational modifications. This review highlights how through bridging material engineering and cellular mechanics, mechanobiology provides a unified framework to understand how physical forces shape tissues and drive pathologies. The continued integration of advanced biomaterials, dynamic biodevices, and multiscale analytical methods promises to uncover new mechanistic insights and inform the development of mechanotherapeutic strategies.
    Keywords:  3D printing; YAP/TAZ; biodevices; biomaterials; cell metabolism; differentiation; mechanosensing; mechanotransduction; organelles; roughness; stem cells; stiffness
    DOI:  https://doi.org/10.3390/biom15060848
  26. Macromol Rapid Commun. 2025 Jun 22. e00304
    Acid-Adaptive Polymers Capable of Proton-Capturing and Matrix-Strengthening.
    Haixu Du, Haoxiang Deng, Di Liu, Qiming Wang.
       BACKGROUND: Biological systems exhibit a remarkable ability to turn destructive environmental stressors into constructive factors for adaptation and survival-a capability rarely observed in engineering materials. Conventional polymers, for instance, degrade in acidic environments as chemical bond cleavage leads to significant loss of stiffness and strength. In contrast, acid-resistant bacteria such as Escherichia coli and Lactococcus lactis neutralize protons and undergo biochemical adaptations to withstand acidity.
    OBJECTIVE: Inspired by natural acid adaptation, we develop an acid-adaptive polymer with exceptional acid resistance and a unique acid-triggered mechanical restoration behavior.
    METHODS: By incorporating sodium carboxylate and amino functional groups, the polymer effectively neutralizes protons, mitigating acid-induced degradation. Besides, invading acids facilitate amidation reactions at temperatures as low as 40°C, forming secondary crosslinks within the polymer matrix.
    RESULTS: This process enhances the material's stiffness and strength by 119% and 101%, respectively.
    CONCLUSION: With its dual functionality of proton neutralization and strength restoration, this polymer offers a transformative solution for defense, chemical processing, and automotive applications requiring durability in harsh acidic environments.
    Keywords:  acid‐resistance; bio‐inspiration; constructive adaptation; mechanical restoration
    DOI:  https://doi.org/10.1002/marc.202500304
  27. Nat Methods. 2025 Jun 26.
    CryoDRGN-AI: neural ab initio reconstruction of challenging cryo-EM and cryo-ET datasets.
    Axel Levy, Rishwanth Raghu, J Ryan Feathers, Michal Grzadkowski, Frédéric Poitevin, Jake D Johnston, Francesca Vallese, Oliver Biggs Clarke, Gordon Wetzstein, Ellen D Zhong.
      Proteins and other biomolecules form dynamic macromolecular machines that are tightly orchestrated to move, bind and perform chemistry. Cryo-electron microscopy and cryo-electron tomography can access the intrinsic heterogeneity of these complexes and are therefore key tools for understanding their function. However, three-dimensional reconstruction of the collected imaging data presents a challenging computational problem, especially without any starting information, a setting termed ab initio reconstruction. Here we introduce cryoDRGN-AI, a method leveraging an expressive neural representation and combining an exhaustive search strategy with gradient-based optimization to process challenging heterogeneous datasets. Using cryoDRGN-AI, we reveal new conformational states in large datasets, reconstruct previously unresolved motions from unfiltered datasets and demonstrate ab initio reconstruction of biomolecular complexes from in situ data. With this expressive and scalable model for structure determination, we hope to unlock the full potential of cryo-electron microscopy and cryo-electron tomography as a high-throughput tool for structural biology and discovery.
    DOI:  https://doi.org/10.1038/s41592-025-02720-4
  28. Small. 2025 Jun 25. e2504261
    Confinement Suppresses Mechanical Force-Mediated Cancer Cell Apoptosis.
    Alka Kumari, Akshay Kumar, Gao Xu, Kaustav Roy, Rudra Pratap, Andrew Holle, Ajay Tijore.
      During the invasion, cancer cells migrate through '3D channel-like tracks' present in the tissues' interstitial extracellular matrix (ECM). Cancer cell migration through these 3D confined channels leads to confinement-induced cell deformation. Emerging reports show that cancer cells are susceptible to mechanical stretch/ultrasound (US)-mediated mechanical forces and undergo calcium-dependent apoptosis (mechanoptosis) under conditions that promote normal cell growth. Surprisingly, we find that confinement-induced cell deformation suppresses mechanoptosis. Studies done using microchannel platforms and tumor spheroid models show that a low level of apoptosis is observed in confined cells. Further, apoptosis level is found to increase with a decrease in the degree of confinement. The absence of mature focal adhesions (FAs), low myosin IIA contractility, and diffuse mechanosensitive Piezo1 channels are responsible for a low level of apoptosis in confined cells. Thus, these findings suggest that confined cells, due to the absence of mature FAs, could not sense and transduce the mechanical forces and generate enough myosin IIA contractility required to initiate apoptosis. The combined action of US and activators of myosin contractility can be used to target invading cancer cells.
    Keywords:  apoptosis; confinement; low‐frequency ultrasound; mechanotransduction; piezo1
    DOI:  https://doi.org/10.1002/smll.202504261
  29. Curr Biol. 2025 Jun 23. pii: S0960-9822(25)00443-9. [Epub ahead of print]35(12): R626-R637
    The cellular substrate of evolutionary novelty.
    Joseph Parker, Matt Pennell.
      A major challenge in biology is comprehending how complex multicellular novelties evolve. Central to this problem is explaining how qualitatively new phenotypic traits - typically the focus of comparative developmental and macroevolutionary studies above the species level - can become established through population genetic processes. Here, we suggest that a resolution may be found by acknowledging the fundamental entities from which functional organismal phenotypes are constructed. We argue that these are not genes, proteins or cell types, but rather gene expression programs (GEPs): sets of co-expressed transcripts that collectively encode cellular subfunctions. We advance that, because GEPs are the smallest, elemental functional units underlying phenotypes, it follows that they represent the substrate upon which population genetic processes must act to explain the origin of evolutionary novelty at the cellular level and above. Novelty arises through the evolution of novel GEPs, through novel synergisms between GEPs that become co-expressed within the same cell or through interactions between different GEPs juxtaposed in cooperating cells within organs. The revolution in single cell biology offers the chance to trace evolution at the resolution of GEPs in populations and across clades, potentially unifying our view of multicellular phenotypic evolution.
    DOI:  https://doi.org/10.1016/j.cub.2025.04.014
  30. RSC Chem Biol. 2025 Jun 19.
    Regulation of bacterial phosphorelay systems.
    Daniel M Foulkes, Daniel M Cooper, Catherine Westland, Dominic P Byrne.
      In terms of biomass, bacteria are the most successful organisms on earth. This is partly attributed to their tremendous adaptive capabilities, which allows them to sense and rapidly organise responses to changing environmental stimuli. Using complex signalling mechanisms, bacteria can relay cellular information to fine-tune their metabolism, maintain homeostasis, and trigger virulence processes during infection. Across all life, protein phosphorylation represents the most abundant signalling mechanism, which is controlled by a versatile class of enzymes called protein kinases and their cognate phosphatases. For many years, histidine kinase (HK)-containing two-component systems (TCSs) were considered the canonical instruments of bacterial sensing. However, advances in metagenomics has since proven that bacterial phosphorelay is in fact orchestrated by a functionally diverse array of integrated protein kinase types, including Ser, Thr, Tyr and Arg-targeting enzymes. In this review, we provide an up-to-date appraisal of bacterial kinase signalling, with an emphasis on how these sensing pathways are regulated to modulate kinase output. Finally, we explore how selective kinase inhibitors may be exploited to control infections and combat the looming health emergency of multidrug resistant bacteria.
    DOI:  https://doi.org/10.1039/d5cb00016e
  31. Curr Top Dev Biol. 2025 ;pii: S0070-2153(25)00014-6. [Epub ahead of print]164 29-65
    Outside influences: The impact of extracellular matrix mechanics on cell migration.
    Ronen Zaidel-Bar, Priti Agarwal.
      "No cell is an island" - highlights the interconnectedness of cellular behavior and the extracellular matrix (ECM). Cell migration is inherently contextual, as cells navigate and adapt to their environments, reshaping the ECM while being influenced by its properties. This review focuses on the mechanical characteristics of the ECM-specifically its architecture, porosity, dynamics, and stiffness-and how these attributes affect cell behavior and migration strategies. We discuss how the mechanical properties are modulated by the composition and arrangement of ECM components and the role of enzymatic activities, including crosslinking and matrix metalloproteinases. By presenting examples from vertebrate and invertebrate developmental models, we demonstrate how ECM mechanics dictate cell migration at various biological scales. Additionally, we examine the importance of cell-matrix adhesions in regulating migration speed and direction. While in vitro studies have advanced our understanding of the molecular mechanisms at play, significant questions persist regarding the regulation of cell migration by ECM mechanics in vivo. Ultimately, this synthesis aims to illuminate the complexities of cell-ECM mechanical interactions, pointing the way for future research that may unveil novel insights into how ECM mechanics influences cell migration during development and disease.
    Keywords:  Basement membrane; Cell migration; Cell-matrix interaction; Development; Extracellular matrix; Extracellular matrix architecture; Extracellular matrix dynamics; Extracellular matrix porosity; Extracellular matrix stiffness; Integrins; Matrix metalloproteases; Mechanosensing; Organogenesis; Tissue morphogenesis
    DOI:  https://doi.org/10.1016/bs.ctdb.2025.01.003
  32. Biopolymers. 2025 Jul;116(4): e70037
    Elucidating Mechanisms of Gelation, Fiber Assembly, and Stability of Injectable Decellularized Extracellular Matrix Biomaterials.
    Alexander Chen, Michael B Nguyen, Julian Cheng, Benjamin D Bridgelal, Kate E Reimold, Joshua Tesoro, Estefania Encisco-Pelayo, Karen L Christman.
      Decellularized extracellular matrix (dECM)-based biomaterials have been widely used for their applications in tissue engineering. In particular, pepsin digestion of dECM can be used to generate injectable forms, including ECM hydrogels as well as an intravascularly infusible ECM (iECM). However, fundamental materials characterization of these materials has been limited, and thus little is known about what exactly drives gelation of ECM hydrogels or the conditions for fibril assembly and growth. With this study, we sought to answer a fundamental question on how these materials assemble or gel, as well as a translational question on what storage conditions are suitable for these materials. Here, we used second-harmonic generation and transmission electron microscopy to investigate the mechanism of gelation for ECM hydrogels and the nanofibril assembly of the iECM. Overall, these microscopies revealed the origin and morphology of self-assembly and that type I collagen lateral and longitudinal growth drives ECM hydrogel formation. On the contrary, the iECM preserved the same mechanism for nanofiber assembly without gelation. In terms of translation, ensuring the stability after rehydration is critical for therapeutic injection timing since changes in the material could impact both safety and efficacy. Via microscopy in conjunction with bulk material characterization, we found that dECM formulations are best kept at 4°C for a maximum of 24 h after rehydration in order to maintain their original properties. Overall, this work provides evidence for the type I collagen directed self-assembly within heterogeneous, injectable, decellularized ECM biomaterials and also determines clinically relevant material storage conditions.
    Keywords:  decellularized extracellular matrix; hydrogel; intravascular; self‐assembly
    DOI:  https://doi.org/10.1002/bip.70037
  33. Sci Adv. 2025 Jun 27. 11(26): eadu5451
    Autonomous chemo-metabolic construction of anisotropic cell-in-shell nanobiohybrids in enzyme-powered cell microrobots.
    Nayoung Kim, Sang Yeong Han, Hyeong Bin Rheem, Hojae Lee, Insung S Choi.
      Living organisms use intricate strategies to adapt and survive in response to potentially lethal environment changes. Inspired by cryptobiosis in nature, researchers have pioneered approaches to create cell-in-shell nanobiohybrids, aiming to endow cells with enhanced protection and exogenous functions. Yet, these methods still lack the biological autonomy intrinsic to natural cellular responses. Here, we present an innovative chemo-metabolically coupled strategy for the autonomous construction of cell-in-shell structures in cell growth medium. Our system harnesses ethanol fermentation by Saccharomyces cerevisiae, chemically coupled with an enzymatic cascade involving alcohol oxidase and horseradish peroxidase, to drive the nanoshell formation of polydopamine. The integration of autonomous shell formation with cellular proliferation produces anisotropic cell-in-shell structures, which can serve as enzyme-powered cell microrobots, upon conjugation with urease. Our autonomous system enables the creation of cell-in-shell nanobiohybrids with dynamic and adaptive environmental interactions, paving the way for transformative applications in synthetic biology, such as artificial cells, as well as advancements in cell-based therapies.
    DOI:  https://doi.org/10.1126/sciadv.adu5451
  34. Mater Horiz. 2025 Jun 26.
    High-performance yet sustainable epoxy composites: from Diels-Alder chemistry to hydrazinolytic degradation.
    Song Gu, Jia-Xin Zhao, Shi-Huan Tan, Yan-Fang Xiao, Yu-Zhong Wang, Li Chen.
      Carbon fiber-reinforced epoxy composites, extensively used in high-performance applications, face significant challenges regarding their recyclability and fire safety. Phosphorus-containing dynamic covalent chemistry offers an effective strategy to address these issues. However, integrating these bonds into either the starting resins or curing agents of epoxy systems typically necessitates complex multi-step syntheses, leading to economic concerns. In this study, we propose a novel one-pot process that simultaneously builds dynamic networks via the phosphonate-containing Diels-Alder (DA) reaction and forms permanent ones via the curing reaction of amine-epoxy system. This innovative approach markedly simplifies the production process, eliminating the need for complex syntheses and additional separation/purification steps, thereby reducing costs and enhancing economic efficiency. The resultant composites exhibit superb flame retardancy, and favorable thermal and mechanical properties. Furthermore, inspired by the Gabriel synthesis, we are the first to employ hydrazinolysis to selectively cleave bonds in DA-based epoxy composite systems, facilitating the recycling of intact carbon fibers alongside the valuable monomers such as maleic hydrazide and 1,6-hexanediamine. This one-pot synthesis strategy represents a substantial step forward in the field of sustainable materials, offering a promising and cost-effective solution for the development of high-performance, recyclable composites.
    DOI:  https://doi.org/10.1039/d5mh00332f
  35. Trends Biotechnol. 2025 Jun 20. pii: S0167-7799(25)00210-0. [Epub ahead of print]
    Challenges of alignment in synthetic cell research.
    M G J L Habets, H A E Zwart, M H Smolka.
      Big Science projects are often troubled by misalignments. We analyze how synthetic cell researchers handle misalignments by performing alignment work. We find that alignment work renders Big Science feasible, but involves trade-offs, for example between short-term successes and long-term goals. We thus recommend attending to the politics of alignment work.
    Keywords:  Big Science; alignment work; synthetic cells
    DOI:  https://doi.org/10.1016/j.tibtech.2025.05.024
  36. Nat Genet. 2025 Jun 27.
    How and when organisms edit their own genomes.
    Vincent C T Hanlon, Alex Cagan, Sebastian Eves-van den Akker.
      Mutations are often thought of as untargeted and non-adaptive, but in rare cases, organisms perform programmed, targeted and adaptive rearrangements of their own DNA sequences. Notable examples include the somatic diversification of immunoglobulin genes, which is the foundation of the vertebrate immune system, and natural CRISPR spacer arrays in bacteria, which recognize and cleave foreign DNA. These systems, along with a dozen known analogs scattered across the tree of life, often underlie critical biological functions, particularly in host-pathogen conflicts. In this Review, we compare the mechanisms by which organisms edit their own genomes. We show that superficially dissimilar editing systems often rely on surprisingly similar genetic mechanisms, regardless of function or taxon. Finally, we argue that the recurrence of editing in host-pathogen conflicts and the bias to a handful of well-studied organisms strongly suggest that new editing systems will be found in understudied pathogens and their hosts.
    DOI:  https://doi.org/10.1038/s41588-025-02230-1
  37. ACS Synth Biol. 2025 Jun 24.
    UV-Resistant Cell-Free Reactions with Synthetic Melanin Additives.
    Lauren M Irie, Dylan M Brown, Julius B Lucks, Nathan C Gianneschi.
      Escherichia coli lysate-based cell-free systems have gained traction for a variety of point-of-use biological applications. Lysate-based cell-free reactions can be freeze-dried, deployed without requiring cold chain, and have a high ease of use through simple rehydration. To maximize their potential, it is of interest to stabilize these reactions to withstand a variety of conditions for long-term storage and use, including stabilization to UV exposure. To address this issue and aid in point-of-use applications, we investigate the use of synthetic melanin nanoparticles as UV-protective additives that are compatible with cell-free reactions. These particles have broadband absorption properties and radical scavenging activity that allow for protection from free radical generation during prolonged UV exposure. Stabilizing cell-free reactions in this way may prolong the stability for use in the field where exposure to sunlight is inevitable.
    Keywords:  allomelanin; cell-free protein synthesis; cell-free systems; eumelanin; melanin nanoparticles; point-of-use manufacturing
    DOI:  https://doi.org/10.1021/acssynbio.5c00212
  38. Nat Phys. 2025 ;21(6): 999-1008
    Interplay of actin nematodynamics and anisotropic tension controls endothelial mechanics.
    Claire A Dessalles, Nicolas Cuny, Arthur Boutillon, Paul F Salipante, Avin Babataheri, Abdul I Barakat, Guillaume Salbreux.
      Blood vessels expand and contract actively as they continuously experience dynamic external stresses from blood flow. The mechanical response of the vessel wall is that of a composite material: its mechanical properties depend on its cellular components, which change dynamically as the cells respond to external stress. Mapping the relationship between these underlying cellular processes and emergent tissue mechanics is an ongoing challenge, particularly in endothelial cells. Here we assess the mechanics and cellular dynamics of an endothelial tube using a microstretcher that mimics the native environment of blood vessels. The characterization of the instantaneous monolayer elasticity reveals a strain-stiffening, actin-dependent and substrate-responsive behaviour. After a physiological pressure increase, the tissue displays a fluid-like expansion, with the reorientation of cell shape and actin fibres. We introduce a mechanical model that considers the actin fibres as a network in the nematic phase and couples their dynamics with active and elastic fibre tension. The model accurately describes the response to the pressure of endothelial tubes.
    Keywords:  Biological physics; Soft materials
    DOI:  https://doi.org/10.1038/s41567-025-02847-3
  39. Nat Mater. 2025 Jun 26.
    Cytoplasmic anillin and Ect2 promote RhoA/myosin II-dependent confined migration and invasion.
    Avery T Tran, Emily O Wisniewski, Panagiotis Mistriotis, Konstantin Stoletov, Maria Parlani, Alice Amitrano, Brent Ifemembi, Se Jong Lee, Kaustav Bera, Yuqi Zhang, Soontorn Tuntithavornwat, Alexandros Afthinos, Alexander Kiepas, Bhawana Agarwal, Sanjiban Nath, John J Jamieson, Yi Zuo, Daniel Habib, Pei-Hsun Wu, Stuart S Martin, Sharon Gerecht, Luo Gu, John D Lewis, Petr Kalab, Peter Friedl, Konstantinos Konstantopoulos.
      Cell migration in mechanically confined environments is a crucial step of metastatic cancer progression. Nonetheless, the molecular components and processes mediating such behaviour are still not fully understood. Here we demonstrate that a pool of the scaffolding protein anillin and its cofactor Ect2, which are both predominantly nuclear proteins and critical mediators of cytokinesis, is present in the cytoplasm of multiple interphase cell types that promote confined cell migration. Confined migration in biomimetic microfluidic models triggers the actomyosin-binding-dependent recruitment of anillin to the plasma membrane at the poles of migrating cells in a manner that scales with microenvironmental stiffness and confinement. The guanine nucleotide exchange activity of Ect2 is required for its RhoA-GTPase-mediated activation of myosin II at the cell poles, enhancing invasion, bleb-based migration and extravasation. Confinement-induced nuclear envelope rupture further amplifies this process due to the release of further anillin and Ect2 into the cytoplasm. Overall, these results show how Ect2 and anillin cooperate to mediate RhoA/ROCK/myosin II-dependent mechanoadaptation and invasive cancer progression.
    DOI:  https://doi.org/10.1038/s41563-025-02269-9
  40. bioRxiv. 2025 Feb 27. pii: 2025.02.27.640614. [Epub ahead of print]
    Immunization with peptide encapsulated within synthetic spores activates T cell responses and reduces tumor growth.
    Domenico D'Atri, Elena Tondini, Federico Machinandiarena, Minsuk Kong, Alilin Mia, Devorah Gallardo, Kandice Tanner, Stephen M Hewitt, David J Fitzgerald, Kumaran S Ramamurthi.
      Peptide-based therapeutic immunizations represent safe approaches to elicit antigen-specific T cell responses, but their broad utility remains limited due to poor immunogenicity and short in vivo stability due to rapid degradation and clearance. Here we employed synthetic bacterial spore-like particles, "SSHELs", made entirely of biocompatible materials, to deliver a model peptide antigen in the absence of additional adjuvants. SSHELs carrying the peptide antigen were internalized by dendritic cells and SSHEL-delivered peptides were then processed and cross-presented in vitro and in vivo more efficiently than free peptides. Further, SSHEL-delivered peptides elicited effective antigen-specific T cell expansion in a manner that was dependent on particle size and peptide presentation mode (encased peptides were superior to surface-attached peptides). In a mouse melanoma model expressing the antigen ovalbumin, therapeutic immunization reduced tumor size and increased survival. We propose that SSHELs are a self-adjuvanting peptide delivery system that mimics a natural presentation to elicit a robust immune response.
    DOI:  https://doi.org/10.1101/2025.02.27.640614
  41. ACS Synth Biol. 2025 Jun 24.
    Microbial Dynamic Regulatory Tools: Design, Applications, and Prospects.
    Haibin Qin, Junping Zhou, Aiping Pang, Lianggang Huang, Zhiqiang Liu, Yuguo Zheng.
      Establishing efficient microbial cell factories for the production of functional nutraceuticals, pharmaceuticals, biofuels, and chemical products requires precise regulation to adapt key enzymes and pathway modules. Dynamic regulatory strategies are a promising and effective approach to achieve balanced cell growth and metabolite production. Dynamic regulatory tools, as the executors of regulatory strategies, usually require rationally designed modification strategies to provide libraries of tools with reliable quality. Here, typical dynamic regulatory tools at the DNA level (transcriptional level), the RNA level (post-transcriptional and translational level), and the protein level (post-translational) are presented. The regulatory mechanisms and design modification strategies of each tool are highlighted. Subsequently, strategies for applying regulatory tools to construct dynamic regulatory networks of metabolic pathways are summarized. Finally, the limitations of current dynamic regulatory tools are discussed and future trends are outlooked.
    Keywords:  dynamic regulatory tools; genetic circuits; metabolic engineering; microbial cell factories; synthetic biology
    DOI:  https://doi.org/10.1021/acssynbio.5c00219
  42. Langmuir. 2025 Jun 27.
    Tuning Biomaterial Surfaces to Modulate Host-Immune Reactions.
    Shalini Pandey, Patrick Bednarz, Omid Veiseh.
      Recent advancements in surface engineering have redefined the design of biomaterial implants, offering new strategies for controlling the immune response and improving device performance. In this review, we examine an array of approaches for modulating the host's foreign body response through surface modifications, including topographical alterations, mechanical tuning, and chemical modification. We detail how these strategies influence cell adhesion, protein adsorption, and macrophage behavior, ultimately reducing the level of fibrosis. Special focus is placed in this review on two principal strategies: zwitterionic coatings that reduce protein fouling and triazole-based modifications that modulate immune cell activity. We also examine recent efforts to integrate these paradigms and highlight how engineered surfaces can alter lipid depositions, revealing new insights into the foreign body response. Ultimately, these insights pave the way for next-generation biomaterial implants while accentuating the ongoing need to unravel the physiochemical relationship between engineered surfaces and immune dynamics in order to achieve clinical success.
    DOI:  https://doi.org/10.1021/acs.langmuir.5c01344
  43. Nat Biomed Eng. 2025 Jun 27.
    Scalable production of human cortical organoids using a biocompatible polymer.
    Genta Narazaki, Yuki Miura, Sergey D Pavlov, Mayuri Vijay Thete, Julien G Roth, Merve Avar, Sungchul Shin, Ji-Il Kim, Zuzana Hudacova, Sarah C Heilshorn, Sergiu P Pașca.
      The generation of neural organoids from human pluripotent stem cells holds great promise in modelling disease and screening drugs, but current approaches are difficult to scale due to undesired organoid fusion. Here we develop a scalable cerebral cortical organoid platform by screening biocompatible polymers that prevent the fusion of organoids cultured in suspension. We identify a cost-effective polysaccharide that increases the viscosity of the culture medium, significantly enhancing the yield of cortical organoids while preserving key features such as regional patterning, neuronal morphology and functional activity. We further demonstrate that this platform enables straightforward screening of 298 FDA-approved drugs and teratogens for growth defects using over 2,400 cortical organoids, uncovering agents that disrupt organoid growth and development. We anticipate this approach to provide a robust and scalable system for modelling human cortical development, and facilitate efficient compound screening for neuropsychiatric disorders-associated phenotypes.
    DOI:  https://doi.org/10.1038/s41551-025-01427-3
  44. Nat Commun. 2025 Jun 25. 16(1): 5389
    Structure of lymphostatin, a large multi-functional virulence factor of pathogenic Escherichia coli.
    Matthias Griessmann, Tim Rasmussen, Vanessa J Flegler, Christian Kraft, Ronja Schneider, Max Hateley, Lukas Spantzel, Mark P Stevens, Michael Börsch, Bettina Böttcher.
      Lymphostatin is a key virulence factor of enteropathogenic and enterohaemorrhagic Escherichia coli, playing roles in bacterial colonisation of the gut and in the inhibition of lymphocyte proliferation and proinflammatory responses. The protein's glycosyltransferase and cysteine protease motifs are required for activity against lymphocytes, but high-resolution structural information has proven elusive. Here, we describe the structure of lymphostatin from enteropathogenic E. coli O127:H6, determined by electron cryo-microscopy at different pH values. We observe three conformations of a highly complex molecule with two glycosyltransferase domains, one PaToxP-like protease domain, an ADP-ribosyltransferase domain, a vertex domain and a delivery domain. Long linkers hold these domains together and occlude the catalytic sites of the N-terminal glycosyltransferase and protease domains. Lymphostatin binds to bovine T-lymphocytes and HEK-293T cells, forming clusters at the plasma membrane that are internalized. With six distinct domains, lymphostatin can be regarded as a multitool of pathogenic Escherichia coli, enabling complex interactions with host cells.
    DOI:  https://doi.org/10.1038/s41467-025-60995-9
  45. Nat Chem Biol. 2025 Jun 23.
    A class of benzofuranoindoline-bearing heptacyclic fungal RiPPs with anticancer activities.
    Qiuyue Nie, Fanglong Zhao, Xuerong Yu, Mithun C Madhusudhanan, Caleb Chang, Siting Li, Sandipan Roy Chowdhury, Bryce Kille, Andy Xu, Rory Sharkey, Chunxiao Sun, Hongzhi Zeng, Shuai Liu, Dishu Zhou, Xin Yu, Kevin Yang, Sandra A C Figueiredo, Maria Zotova, Zichen Hu, Alan Y Du, Dongyin Guan, Rui Tang, Todd Treangen, Jin Wang, Pedro N Leão, Yang Gao, Junjie Chen, Peng Liu, Hans Renata, Xue Gao.
      Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a promising source of new pharmaceuticals, yet the therapeutic potential of fungal RiPPs remains largely underexplored. Here we report asperigimycins as a distinct class of fungal RiPPs, featuring a unique heptacyclic scaffold consisting of a benzofuranoindoline core and three additional macrocycles, primarily assembled by six distinct fungi-specific DUF3328 oxidases. Inspired by the enhancement of anticancer activity through the N-terminal pyroglutamate in naturally occurring asperigimycins C and D, we chemically modify the inactive asperigimycin B with a series of lipid substitutions at its N-terminus. A derivative with a C-11 linear fatty acid, 2-L6, achieves nanomolar anticancer potency comparable to that of clinically approved antileukemia drugs. High-throughput CRISPR screening identifies the SLC46A3 transporter as a critical factor mediating 2-L6 cellular uptake into human cells. Our findings highlight the promise of engineering asperigimycins as therapeutic leads for cancer treatment.
    DOI:  https://doi.org/10.1038/s41589-025-01946-9
  46. mBio. 2025 Jun 25. e0395424
    Mammalian fatty acid synthase: a commonly used viral host dependency factor and a putative target for host-targeted broad-spectrum antiviral therapeutic development.
    Paola N Loperena González, Krithika P Karthigeyan, Jacqueline Corry, Anurup Krishna, Ben Hackenberg, Beatriz Sierra, Jesse J Kwiek.
      Viruses regulate host processes to create cellular environments favorable to viral replication. At least 27 viruses that infect humans require host fatty acid synthase (FASN)-dependent de novo fatty acid biosynthesis, including viruses from the Coronaviridae, Flaviviridae, Herpesviridae, Picornaviridae, Retroviridae, and Togaviridae families. How could FASN activity and subsequent de novo fatty acid production impact viral replication? FASN activity produces the fatty acid palmitate, which can be further metabolized into fatty acids that are used to form lipid droplets that can be used during viral assembly and budding, for beta-oxidation to generate ATP, and to create fatty acyl groups used for post-translational protein modification to change the subcellular localization of viral or host proteins. In this minireview, we outline the function of FASN, review the mechanisms linking virus replication and fatty acid biosynthesis, and consider the potential of FASN as a target for broad-spectrum antiviral drug development.
    Keywords:  FASN; antiviral pharmacology; coronavirus; flavivirus; virus-host interactions
    DOI:  https://doi.org/10.1128/mbio.03954-24
  47. Metab Eng. 2025 Jun 17. pii: S1096-7176(25)00094-1. [Epub ahead of print]
    Kinetic-model-guided engineering of multiple S. cerevisiae strains improves p-coumaric acid production.
    Bharath Narayanan, Wei Jiang, Shengbao Wang, Javier Sáez-Sáez, Daniel Weilandt, Maria Masid Barcon, Viktor Hesselberg-Thomsen, Irina Borodina, Vassily Hatzimanikatis, Ljubisa Miskovic.
      The use of kinetic models of metabolism in design-build-learn-test cycles is limited despite their potential to guide and accelerate the optimization of cell factories. This is primarily due to difficulties in constructing kinetic models capable of capturing the complexities of the fermentation conditions. Building on recent advances in kinetic-model-based strain design, we present the rational metabolic engineering of an S. cerevisiae strain designed to overproduce p-coumaric acid (p-CA), an aromatic amino acid with valuable nutritional and therapeutic applications. To this end, we built nine kinetic models of an already engineered p-CA-producing strain by integrating different types of omics data and imposing physiological constraints pertinent to the strain. These nine models contained 268 mass balances involved in 303 reactions across four compartments and could reproduce the dynamic characteristics of the strain in batch fermentation simulations. We used constraint-based metabolic control analysis to generate combinatorial designs of 3 enzyme manipulations that could increase p-CA yield on glucose while ensuring that the resulting engineering strains did not deviate far from the reference phenotype. Among 39 unique designs, 10 proved robust across the phenotypic uncertainty of the models and could reliably increase p-CA yield in nonlinear simulations. We implemented these top 10 designs in a batch fermentation setting using a promoter-swapping strategy for down-regulations and plasmids for up-regulations. Eight out of the ten designs produced higher p-CA titers than the reference strain, with 19 - 32% increases at the end of fermentation. All eight designs also maintained at least 90% of the reference strain's growth rate, indicating the critical role of the phenotypic constraint. The high experimental success of our in-silico predictions lays the foundation for accelerated design-build-test-learn cycles enabled by large-scale kinetic modeling.
    DOI:  https://doi.org/10.1016/j.ymben.2025.06.008
  48. Sci Adv. 2025 Jun 27. 11(26): eadw6814
    Sequestration of ribosome biogenesis factors in HSV-1 nuclear aggregates revealed by spatially resolved thermal profiling.
    Peter J Metzger, Tavis J Reed, Krystal K Lum, Jordy F Botello, Lifei Jiang, Clifford P Brangwynne, Olga G Troyanskaya, Ileana M Cristea.
      Viruses exploit host cell reliance on compartmentalization to facilitate their replication. Herpes simplex virus type 1 (HSV-1) modulates the subcellular localization of host proteins to suppress immune activation, license viral gene expression, and achieve translational shutoff. To spatially resolve dynamic protein-protein interaction (PPI) networks during infection with an immunostimulatory HSV-1 strain, we integrated nuclear/cytoplasmic fractionation with thermal proximity coaggregation analysis (N/C-TPCA). The resulting expanded depth and spatial resolution of PPIs charted compartment-specific assemblies of protein complexes throughout infection. We find that a broader suite of host chaperones than previously anticipated exhibits nuclear recruitment to form condensates known as virus-induced chaperone-enriched (VICE) domains. Monitoring protein and RNA constituents and ribosome activity, we establish that VICE domains sequester ribosome biogenesis factors from ribosomal RNA, accompanying a cell-wide defect in ribosome supply. These findings highlight infection-driven VICE domains as nodes of translational remodeling and demonstrate the utility of N/C-TPCA to study dynamic biological contexts.
    DOI:  https://doi.org/10.1126/sciadv.adw6814
  49. J Food Sci. 2025 Jun;90(6): e70350
    Development of Polysaccharide Hydrogels Enriched With Protein and Starch for Bovine Myoblast Cell Culture.
    Jihad Kamel, Jun-Yeong Lee, Usha Yadav, Sadia Afrin, Chandra-Jit Yadav, Sun Mi Zo, Sung Soo Han, Kyung-Mee Park.
      The expanding worldwide population has increased the meat demand, prompting efforts to find alternatives. A promising approach is the cultivation of animal cells on edible biomaterials for cultured meat production. However, those biomaterials face challenges in their mechanical properties, cytotoxicity, and ability to support optimal cell growth. In this study, we focused on optimizing plant-edible hydrogels as a 3D environment for the growth of bovine myoblast cells. We prepared alginate hydrogel (A) to be enriched with soybean protein (S.A) and tapioca starch (T.A), developing Group 1 hydrogels. Aiming to enhance their elasticity, xanthan gum (XG) was incorporated into Group 1, generating alginate-xanthan gum (Ax), soybean-alginate-xanthan gum (S.Ax), and tapioca-alginate-xanthan gum (T.Ax) Group 2 hydrogels. Both groups were assessed for physical and chemical analyses, rheological testing, cell viability assays, immunofluorescence staining, gene expression, and flavor profiling. Our findings showed that all hydrogels maintained their crosslinking for up to 7 days except Ax and T.Ax, which showed degradation of 57.39% and 36.03%, respectively. Both groups represented swelling characteristics, porosity, protein adsorption, and cooking capabilities. Moreover, A and S.A exhibited viscous properties with slow stress relaxation, whereas T.A displayed rapid relaxation and viscoelastic behavior. Successfully, Group 2 demonstrated faster stress relaxation and sufficient elasticity. Bovine myoblast cells showed no significant toxicity and could proliferate, expressing paired box 7 (PAX-7) marker in both groups. At the differentiation stage, desmin expression indicated the intermediate differentiation of the muscle cells for up to 7 days in both groups. Besides S.A and S.Ax scaffolds exhibit the nearest metabolic similarity to beef among the plant-based scaffolds. These findings suggest that the hydrogels enriched with protein and starch holding the potential for culture meat production.
    Keywords:  alginate hydrogel; bovine myoblasts; culture meat; xanthan gum
    DOI:  https://doi.org/10.1111/1750-3841.70350
  50. Micromachines (Basel). 2025 May 29. pii: 654. [Epub ahead of print]16(6):
    Bioprinting of GelMA-Based Hydrogels to Aid in Creation of Biomimetic 3D Models for Glioblastoma.
    Kaitlyn Ann Rose Schroyer, Kylie Marie Schmitz, Gunjeeta Raheja, Bin Su, Justin D Lathia, Liqun Ning.
      Glioblastoma (GBM, isocitrate dehydrogenase wild-type) is the most common primary malignant brain tumor in adults and is associated with a severely low survival rate. Treatments offer mere palliation and are ineffective, due, in part, to a lack of understanding of the intricate mechanisms underlying the disease, including the contribution of the tumor microenvironment (TME). Current GBM models continue to face challenges as they lack the critical components and properties required. To address this limitation, we developed innovative and practical three-dimensional (3D) GBM models with structural and mechanical biomimicry and tunability. These models allowed for more accurate emulation of the extracellular matrix (ECM) and vasculature characteristics of the native GBM TME. Additionally, 3D bioprinting was utilized to integrate these complexities, employing a hydrogel composite to mimic the native environment that is known to contribute to tumor cell growth. First, we examined the changes in physical properties that resulted from adjoining hydrogels at diverse concentrations using Fourier-Transform Infrared Spectroscopy (FTIR), compression testing, scanning electron microscopy (SEM), rheological analysis, and degradation analysis. Subsequently, we refined and optimized the embedded bioprinting processes. The resulting 3D GBM models were structurally reliable and reproducible, featuring integrated inner channels and possessing tunable properties to emulate the characteristics of the GBM ECM. Biocompatibility testing was performed via live/dead and AlamarBlue analyses using GBM cells (both commercial cell lines and patient-derived cell lines) encapsulated in the constructs, along with immunohistochemistry staining to understand how ECM properties altered the functions of GBM cells. The observed behavior of GBM cells indicated greater functionality in softer matrices, while the incorporation of hyaluronic acid (HA) into the gelatin methacryloyl (gelMA) matrix enhanced its biomimicry of the native GBM TME. The findings underscore the critical role of TME components, particularly ECM properties, in influencing GBM survival, proliferation, and molecular expression, laying the groundwork for further mechanistic studies. Additionally, the outcomes validate the potential of leveraging 3D bioprinting for GBM modeling, providing a fully controllable environment to explore specific pathways and therapeutic targets that are challenging to study in conventional model systems.
    Keywords:  3D bioprinting; GBM modeling; extracellular matrix; glioblastoma; hydrogels; tumor microenvironment
    DOI:  https://doi.org/10.3390/mi16060654
  51. Adv Sci (Weinh). 2025 Jun 25. e07060
    Programmable DNA-Based Molecular Neural Network Biocomputing Circuits for Solving Partial Differential Equations.
    Yijun Xiao, Alfonso Rodríguez-Patón, Jianmin Wang, Pan Zheng, Tongmao Ma, Tao Song.
      Partial differential equations, essential for modeling dynamic systems, persistently confront computational complexity bottlenecks in high-dimensional problems, yet DNA-based parallel computing architectures, leveraging their discrete mathematics merits, provide transformative potential by harnessing inherent molecular parallelism. This research introduces an augmented matrix-based DNA molecular neural network to achieve molecular-level solving of biological Brusselator PDEs. Two crucial innovations address existing technological constraints: (i) an augmented matrix-based error-feedback DNA molecular neural network, enabling multidimensional parameter integration through DNA strand displacement cascades and iterative weight optimization; (ii) incorporating membrane diffusion theory with division operation principles into DNA circuits to develop partial differential calculation modules. Simulation results demonstrate that the augmented matrix-based DNA neural network efficiently and accurately learns target functions; integrating the proposed partial derivative computation strategy, this architecture solves the biological Brusselator PDE numerically with errors below 0.02 within 12,500 s. This work establishes a novel intelligent non-silicon-based computational framework, providing theoretical foundations and potential implementation paradigms for future bio-inspired computing and unconventional computing devices in life science research.
    Keywords:  DNA computing; DNA strand displacement reactions; chemical reaction networks (CRNs); neural networks circuits; partial differential equations
    DOI:  https://doi.org/10.1002/advs.202507060
  52. Nat Biotechnol. 2025 Jun 27.
    Improving engineered biological systems with electronics and microfluidics.
    Rabia Tugce Yazicigil, Akshaya Bali, Dilara Caygara, Douglas Densmore.
      Hybrid engineered biological systems integrate electronics and microfluidics with engineered biological components, such as microbes or cell-free DNA-based systems, to effectively sense, act upon and report on biological environments. As these engineered biological systems become essential in addressing challenges in healthcare, environmental monitoring, remediation and agriculture, this Review offers an in-depth discussion of their applications, critical design choices and challenges. Alongside an overview of the state of the field, we present a classification framework aimed at helping researchers make informed and optimized design decisions tailored to the intended biological application. Furthermore, we outline how the development of cyber-secure biological systems could enhance the security and functionality of engineered biological platforms. Last, we introduce a 'Living Roadmap' ( https://www.programmingbiology.org/csbs ) to dynamically reflect the field's progress and support continuous monitoring of future advancements.
    DOI:  https://doi.org/10.1038/s41587-025-02709-6
  53. Biochemistry. 2025 Jun 23.
    Post-Transcriptional Modifications of the Large Ribosome Subunit Assembly Intermediates in E. coli Expressing a Helicase-Inactive DbpA Variant.
    Luis A Gracia Mazuca, Jonathon E Mohl, Samuel S Cho, Eda Koculi.
      RNA post-transcriptional modifications are ubiquitous across all organisms and serve as fundamental regulators of cellular homeostasis, growth, and stress adaptation. Techniques for the simultaneous detection of multiple RNA modifications in a high-throughput, single-nucleotide-resolution manner are largely absent in the field, and developing such techniques is of paramount importance. We used the Escherichia coli ribosome as a model system to develop novel techniques for RNA post-transcriptional modification detection, leveraging its extensive and diverse array of modifications. For modification detection, we quantified the reverse transcriptase deletions and misincorporations at modification positions using Illumina next-generation sequencing. We simultaneously detected the following modifications in ribosomal RNA (rRNA): 1-methylguanosine (m1G), 2-methylguanosine (m2G), 3-methylpseudouridine, N6,N6-dimethyladenosine, and 3-methyluridine, without chemical treatment. Furthermore, subjecting the rRNA samples to 1-cyclohexyl-3-(2-morpholinoethyl) carbodiimide metho-p-toluenesulfonate followed by alkaline conditions allowed us to simultaneously detect pseudouridine, 7-methylguanosine (m7G), 5-hydroxycytidine (OH5C), 2-methyladenosine, and dihydrouridine (D). Finally, subjecting the rRNA samples to KMnO4 followed by alkaline conditions allowed us to simultaneously detect m7G, OH5C, and D. Our results reveal that m1G, m2G, m7G, and D are incorporated prior to the accumulation of the 27S, 35S, and 45S large subunit intermediates in cells expressing the helicase-inactive R331A DbpA construct. These intermediates belong to three distinct stages and pathways of the large subunit ribosome assembly. Therefore, our results identify the time points in three pathways at which m1G, m2G, m7G, and D are incorporated into the large ribosome subunit and provide a framework for broader studies on RNA modification dynamics.
    DOI:  https://doi.org/10.1021/acs.biochem.5c00034
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