bims-enlima Biomed News
on Engineered living materials
Issue of 2025–07–27
47 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool
  1. Massively parallel microbubble nano-assembly.
  2. Nanowhisker glues for fatigue-resistant bioadhesion and interfacial functionalization.
  3. Additive manufacturing of multi-material and hollow structures by Embedded Extrusion-Volumetric Printing.
  4. A genetic safeguard for eliminating target genes in synthetic probiotics in a gut environment.
  5. Open-source tubing-free impeller pump platform for controlled recirculating fluid flow for microfluidics and organs-on-chip.
  6. Made-to-order DNA goes big: new tech doubles size of custom genetic sequences.
  7. High-resolution spatial mapping of cell state and lineage dynamics in vivo with PEtracer.
  8. Functionalities of Simple and Complex Electrolytes in Confinement.
  9. Self-Assembling Aromatic Peptide Amphiphile Fibers for Multivalent Display of Enzymatically Linked Antigenic Proteins.
  10. Tunable Single-Cell Multistate Nanomechanical Phenotyping by Micropipette-Assisted Atomic Force Microscopy to Dissect Cellular Heterogeneity.
  11. Mutualism between degraders and nondegraders stabilizes the function of a natural biopolymer-degrading community.
  12. Mechanical underwater adhesive devices for soft substrates.
  13. 3D printing of hydrogel nanocomposites: A symbiotic union for advanced biomedical applications.
  14. Mannich reaction-based combinatorial libraries identify antioxidant ionizable lipids for mRNA delivery with reduced immunogenicity.
  15. Conditional guide RNA deactivation by mRNA and small molecule triggers in Saccharomyces cerevisiae.
  16. Hydrogel-Immobilized Multienzyme Systems for Cell-Free Chemical Bioproduction.
  17. Genome-scale metabolic modelling of human gut microbes to inform rational community design.
  18. Dynamic Modulation of Multicellular Interactions via ATP-Dissipative DNA Assembly.
  19. Deciphering the assembly process of PQQ dependent methanol dehydrogenase.
  20. Visible Light-Driven Spatiotemporal-Resolved Proton Management by Harnessing Merocyanine-Integrated Hydrogels as Regenerative Photoacid Matrices.
  21. Polysaccharide-based nanoparticles for 3D (bio)printing.
  22. Engineering Cell Fate with Adaptive Feedback Control.
  23. Scalable Biofabrication of Functional 3D Scaffolds via Synergy of Autopilot Single-Jet Electrospun 3D PCL Fiber Scaffolds and Cell-Laden Hydrogels.
  24. Docking domains from modular polyketide synthases and their use in engineering.
  25. Dynamic control of ferroic domain patterns by thermal quenching.
  26. Precise virulence inactivation using a CRISPR-associated transposase for combating Enterobacteriaceae gut pathogens.
  27. Ionically crosslinked biohybrid gelatin-based hydrogels for 3D cell culture.
  28. Systematic Mapping of Bacterial CRISPRa Systems for Synergistic Gene Activation Reveals Antagonistic Effects.
  29. Unveiling the hidden interactome of CRBN molecular glues.
  30. Genetic "expiry-date" circuits control lifespan of synthetic scavenger bacteria for safe bioremediation.
  31. Engineering glycosyltransferases into glycan binding proteins using a mammalian surface display platform.
  32. Engineering a microfluidic-assisted 3D bioprinting approach for the hierarchical control deposition and compartmentalisation of graded bioinks.
  33. A modular model integrating metabolism, growth, and cell cycle predicts that fermentation is required to modulate cell size in yeast populations.
  34. Leveraging chromatin packing domains to target chemoevasion in vivo.
  35. Panorama of Conductive Freestanding Biopolymers for Long-Range Charge Transfer: Effect of Chemical Modification and Doping.
  36. Engineering principles of zwitterionic hydrogels: Molecular architecture to manufacturing innovations for advanced healthcare materials.
  37. ATP synthesis driven by atmospheric hydrogen concentrations.
  38. Bottom-up computational design of shape-selective organic macrocycles for humid CO2 capture.
  39. Precisely defining disease variant effects in CRISPR-edited single cells.
  40. Unrefined plant raw materials are key to nutritious food.
  41. Stimuli-responsive hybrid materials for 4D in vitro tissue models.
  42. In situ interfacial shear rheology of fungal films.
  43. Protocol for assessment of CRISPR base editors and their components in Escherichia coli.
  44. Genetically programmable wearable devices for precision physiological and molecular monitoring.
  45. Cellulosic Functional Bioplastic with Tunable Strength and Toughness Through Heat-Treatment of Dynamic Covalent Networks.
  46. A quorum sensing-controlled type I CRISPRi toolkit for dynamically regulating metabolic flux.
  47. Medical devices: Materials, mechanics, and manufacturing.
  1. Nat Commun. 2025 Jul 22. 16(1): 6743
    Massively parallel microbubble nano-assembly.
    Hyungmok Joh, Bin Lian, Shaw-Iong Hsueh, Zhichao Ma, Keng-Jung Lee, Si-Yang Zheng, Peer Fischer, Donglei Emma Fan.
      Microbubbles are an important tool due to their unique mechanical, acoustic, and dynamical properties. Yet, it remains challenging to generate microbubbles quickly in a parallel, biocompatible, and controlled manner. Here, we present an opto-electrochemical method that combines precise light-based projection with low-energy electrolysis, realizing defined microbubble patterns that in turn trigger assembly processes. The size of the bubbles can be controlled from a few to over hundred micrometers with a spatial accuracy of ~2 μm. The minimum required light intensity is only ~0.1 W/cm2, several orders of magnitude lower compared to other light-enabled methods. We demonstrate the assembly of prescribed patterns of 40-nm nanocrystals, 200 nm extracellular vesicles, polymer nanospheres, and live bacteria. We show how nanosensor-bacterial-cell arrays can be formed for spectroscopic profiling of metabolites and antibiotic response of bacterial assemblies. The combination of a photoconductor with electrochemical techniques enables low-energy, low-temperature bubble generation, advantageous for large-scale, one-shot patterning of diverse particles in a biocompatible manner. The microbubble-platform is highly versatile and promises new opportunities in nanorobotics, nanomanufacturing, high-throughput bioassays, single cell omics, bioseparation, and drug screening and discovery.
    DOI:  https://doi.org/10.1038/s41467-025-62070-9
  2. Nat Commun. 2025 Jul 24. 16(1): 6826
    Nanowhisker glues for fatigue-resistant bioadhesion and interfacial functionalization.
    Shuaibing Jiang, Tony Jin, Tianqin Ning, Zhen Yang, Zhenwei Ma, Ran Huo, Yixun Cheng, Davis Kurdyla, Edmond Lam, Rong Long, Audrey Moores, Jianyu Li.
      Fatigue-resistant functional bioadhesion is desired in diverse applications ranging from wound management to wearable devices. Nanoparticle-based bioadhesives offer versatile functionality but suffer from weak adhesion and fatigue vulnerability due to tissue barriers and poor tissue interactions. Polymer chain-based bioadhesives can form tough bioadhesion but remain vulnerable to fatigue fracture. Here we demonstrate that rationally designed chitosan nanowhiskers glues achieve fatigue-resistant bioadhesion and interfacial functionalization via the combined high aspect ratio, rigidity, polymer-binding and network-forming properties. We deploy these glues using chemical enhancers, microneedle rollers, and ultrasound, enabling strong tissue anchorage despite tissue barriers. At low concentrations, the nanowhisker glue paired with a tough hydrogel achieves an interfacial fatigue threshold of 382 J m-2 and adhesion energy exceeding 1000 J m-2. Transmission electron microscopy reveals a sandwiched nanowhisker layer interpenetrated with both hydrogels and tissues, creating an interface of high stiffness and strength that kinks and arrests interfacial cracks, ensuring unprecedented fatigue resistance. Further, the nanowhisker glue allows for versatile functionalization at the interface such as photothermal and sonodynamic effects. This work expands the performance and functionality of bioadhesives, opening new possibilities for medical and engineering applications.
    DOI:  https://doi.org/10.1038/s41467-025-62019-y
  3. Nat Commun. 2025 Jul 22. 16(1): 6730
    Additive manufacturing of multi-material and hollow structures by Embedded Extrusion-Volumetric Printing.
    Silvio Tisato, Grace Vera, Qingchuan Song, Niloofar Nekoonam, Dorothea Helmer.
      Tomographic volumetric additive manufacturing support-free 3D printing has significantly faster print speed than traditional vat photopolymerization and material extrusion techniques. At the same time, tomographic volumetric additive manufacturing allows the embedding of external objects in the print volume before the print to produce complex multi part assemblies by so-called overprinting. As tomographic volumetric additive manufacturing increases its popularity, more and more of its limitations with regards to available materials are removed, and printing with acrylates, ceramics and glasses has been shown. However, creating multi material parts without resorting to overprinting is still challenging. Here, multi-material tomographic volumetric additive manufacturing printing is presented by combining tomographic volumetric additive manufacturing and Embedded 3D printing: photopolymerizable support baths are used to deposit inks in defined shapes allowing the consecutive definition and volumetric printing of multi-material structures via tomographic volumetric additive manufacturing. We show the fabrication of several multi-material structures with arbitrarily positioned materials, as well as chips with microchannels having diameters lower than 120 µm.
    DOI:  https://doi.org/10.1038/s41467-025-62057-6
  4. iScience. 2025 Aug 15. 28(8): 113027
    A genetic safeguard for eliminating target genes in synthetic probiotics in a gut environment.
    Nhu Nguyen, Miaomiao Wang, Lin Li, Clement T Y Chan.
      To meet the emerging demand for constraining engineered probiotic activities, many biocontainment studies explore strategies that involve killing engineered microbes, which often create basal levels of cytotoxicity that hamper cell fitness and performance. Here, we explored a circuit design that destroys the engineered genetic materials in a probiotic strain, instead of killing these cells, under non-permissive conditions. Our safeguard circuit involves a two-layered transcriptional regulatory circuit to control the expression of a CRISPR system that targets the engineered genes for degradation. In Escherichia coli Nissle 1917 (EcN), the biocontainment system did not hamper cell fitness, and it continuously scavenged and destroyed the target, promoting complete elimination of engineered genetic materials and activities. We demonstrated that the engineered probiotics maintained its activities for 7 days in a mouse model when the permissive signal was supplied constantly, but the activities became undetectable within two days upon the cease of signal supply.
    Keywords:  Applied microbiology; Biomolecular engineering; Microbial genetics; Techniques in genetics
    DOI:  https://doi.org/10.1016/j.isci.2025.113027
  5. HardwareX. 2025 Sep;23 e00673
    Open-source tubing-free impeller pump platform for controlled recirculating fluid flow for microfluidics and organs-on-chip.
    Sophie R Cook, Erin E Lawrence, Parastoo Sakinejad, Rebecca R Pompano.
      Fluid flow is utilized in many microscale technologies, including microfluidic chemical reactors, diagnostics, and organs-on-chip (OOCs). In particular, OOCs may rely on fluid flow for nutrient delivery, cellular communication, and application of shear stress. In order for microscale flow systems to be readily adopted by non-experts, a tubing-free, user-friendly pump would be useful, particularly one that is simple to use, affordable, and compatible with cell culture incubators. To address these needs, here we share the design and fabrication of an impeller pump platform that provides recirculating fluid flow through a microfluidic loop without the need for tubing connections. Flow is driven by rotating a magnetic stir bar or 3D-printed impeller in a pump well, using magnets mounted on a DC motor. The DC motors used produce negligible heat output in a compact system, making it compatible with cell culture incubators. The pump platform accommodates user-defined microfluidic or OOC device geometries, which may be easily customized by 3D printing. Furthermore, the system is easily assembled from low-cost materials and simple circuitry by someone with no prior training. We demonstrate the ability of the platform to drive recirculating fluid flow in a microfluidic device at well-characterized flow velocities ranging from µm/s to mm/s for use with microfluidic technologies. Though designed with OOCs in mind, we envision that this platform will enable users from ranging disciplines to incorporate fluid flow in customized microscale technologies.
    Keywords:  3D printing; Bioreactor; Micropump; Multi-organ-on-chip; Stir bar
    DOI:  https://doi.org/10.1016/j.ohx.2025.e00673
  6. Nature. 2025 Jul;643(8073): 1146-1147
    Made-to-order DNA goes big: new tech doubles size of custom genetic sequences.
    Caroline Seydel.
      
    Keywords:  Chemistry; Molecular biology; Synthetic biology; Technology
    DOI:  https://doi.org/10.1038/d41586-025-02261-y
  7. Science. 2025 Jul 24. eadx3800
    High-resolution spatial mapping of cell state and lineage dynamics in vivo with PEtracer.
    Luke W Koblan, Kathryn E Yost, Pu Zheng, William N Colgan, Matthew G Jones, Dian Yang, Arhan Kumar, Jaspreet Sandhu, Alexandra Schnell, Dawei Sun, Can Ergen, Reuben A Saunders, Xiaowei Zhuang, William E Allen, Nir Yosef, Jonathan S Weissman.
      Charting the spatiotemporal dynamics of cell fate determination in development and disease is a long-standing objective in biology. Here we present the design, development, and extensive validation of PEtracer, a prime editing-based, evolving lineage tracing technology compatible with both single-cell sequencing and multimodal imaging methodologies to jointly profile cell state and lineage in dissociated cells or while preserving cellular context in tissues with high spatial resolution. Using PEtracer coupled with MERFISH spatial transcriptomic profiling in a syngeneic mouse model of tumor metastasis, we reconstruct the growth of individually-seeded tumors in vivo and uncover distinct modules of cell-intrinsic and cell-extrinsic factors that coordinate tumor growth. More generally, PEtracer enables systematic characterization of cell state and lineage relationships in intact tissues over biologically-relevant temporal and spatial scales.
    DOI:  https://doi.org/10.1126/science.adx3800
  8. J Am Chem Soc. 2025 Jul 23.
    Functionalities of Simple and Complex Electrolytes in Confinement.
    Felipe Jiménez-Ángeles, Nicholas Pogharian, Brandon Nicholas Onusaitis, Monica Olvera de la Cruz.
      Understanding simple and molecular electrolytes has advanced the development of various biotechnologies and industrial processes. In recent years, researchers have designed new ion-based architectures that emulate important biomimetic functions such as neural and organelle-like processes to alleviate societal demands. These examples, and many other bioinspired futuristic devices, rely on understanding and controlling electrostatic interactions in nanoscale confinement. For example, information transference and data processing demands have motivated studies toward the development of neuromorphic computers, which could distribute information into many small neuron-like devices that process and store information locally. Another area where the design of biomimetic functions plays a key role is in the need to decompose environmentally harmful chemicals. This has led to the design of synthetic mimics of unstructured proteins to protect enzymes in nonbiological environments, resembling the functions of membraneless organelles. This perspective explores principles aimed to design composite materials involving simple and complex electrolytes in confinement to imitate functional biomaterials. The function of layered materials for the synthesis of ionic machines and of poleylectrolytes to assemble functional enzymatic membranes is discussed, emphasizing new physical chemistry principles and computational methodologies.
    DOI:  https://doi.org/10.1021/jacs.5c04186
  9. ACS Appl Mater Interfaces. 2025 Jul 23.
    Self-Assembling Aromatic Peptide Amphiphile Fibers for Multivalent Display of Enzymatically Linked Antigenic Proteins.
    Rie Wakabayashi, Ghazian Dzaky Syahid Fathullah, Ayato Higuchi, Honggang Cui, Kosuke Minamihata, Noriho Kamiya, Masahiro Goto.
      Supramolecular fibers assembled from peptide amphiphiles are promising materials for the delivery of biopharmaceuticals. However, strategies for directly conjugating folded proteins onto these supramolecular dynamic assemblies remain limited. Herein, we demonstrate that aromatic peptide amphiphiles that integrate self-assembly motifs with enzymatic recognition sequences enable the synthesis of supramolecular fibrous materials amenable to protein conjugation in their native folded state. The designed peptide amphiphiles self-assembled into fibers through a combination of hydrophobic, aromatic, and hydrogen bonding interactions in aqueous media. Using microbial transglutaminase, a recombinant enhanced green fluorescent protein (EGFP), used as a model proteinaceous antigen, was covalently coupled to the fibers via site-specific enzymatic cross-linking. This direct conjugation greatly enhanced the intracellular delivery of EGFP to murine dendritic cells in a manner dependent upon the peptide design. Notably, the resulting conjugates exhibited markedly increased immunogenicity compared to the protein alone, as evidenced by the elevated production of antigen-specific immunoglobulin G. These findings position the conjugated supramolecular fibers as a versatile platform for protein delivery and vaccine development.
    Keywords:  enzymatic reaction; immune material; intracellular protein delivery; peptide amphiphiles; self-assembly
    DOI:  https://doi.org/10.1021/acsami.5c10222
  10. ACS Appl Mater Interfaces. 2025 Jul 22.
    Tunable Single-Cell Multistate Nanomechanical Phenotyping by Micropipette-Assisted Atomic Force Microscopy to Dissect Cellular Heterogeneity.
    Yaqi Feng, Lianqing Liu, Mi Li.
      Mechanical forces are crucial for cellular function and disease, and particularly, atomic force microscopy (AFM)-based force spectroscopy has become a standard and important platform for characterizing the mechanical properties of single cells. Here, we present a study of micropipette-assisted AFM that enables multistate nanomechanical phenotyping of a living cell during its biological processes. Micropipette-assisted AFM offers the additional capability to manipulate single living cells in three dimensions, allowing the utilization of an AFM-based force spectroscopy assay to construct the dynamic nanomechanical phenotypes of single cells at multiple states. With micropipette manipulations, individual living cells could be selectively isolated in situ and subsequently positioned at specific locations on the engineered substrates with controllable properties. Subsequently, the mechanical changes of the same cells in the changed physiological states due to the interactions between cells and their altered microenvironments could be measured by AFM. The effectiveness of the proposed method was verified in a variety of systems, including single-cell responses to ECM biochemical cues, single-cell responses to ECM physical cues, and single-cell mechanics involved in cell-cell interactions within physical confinement, revealing numerous distinctive behaviors and nanomechanical phenotypes of individual cells. The study demonstrates an experimental approach to build the mechanical atlas of single cells undergoing regulated physiological and pathological changes, which offers additional possibilities for dissecting cellular heterogeneity from the biomechanical perspective and will benefit mechanobiology.
    Keywords:  atomic force microscopy; cellular heterogeneity; cell−cell interaction; microenvironmental cue; micropipette manipulation; single-cell mechanical assay
    DOI:  https://doi.org/10.1021/acsami.5c09704
  11. Proc Natl Acad Sci U S A. 2025 Jul 29. 122(30): e2500664122
    Mutualism between degraders and nondegraders stabilizes the function of a natural biopolymer-degrading community.
    Liang Liu, Changfu Tian, Miaoxiao Wang, Ying Luo, Yaru Huang, Tingting Jiang, Hongwen Zhao, Qijun Yu, Entao Wang, Jinshui Yang, Hongli Yuan.
      Natural biopolymer-degrading microbial communities drive carbon biogeochemical cycling. Within these communities, polymer degraders facilitate the growth of nondegraders by breaking down polymers through extracellular enzymes. However, the contributions of nondegraders to community dynamics, as well as the mechanisms that limit their access to degradation products, remain poorly understood. Here, we investigate EMSD5, a lignocellulose-degrading microbial community that efficiently converts corncob into isopropanol. We demonstrate that nondegraders, such as Escherichia coli, enable the growth of degraders (e.g., Lachnoclostridium sp. and Clostridium beijerinckii) by creating anaerobic conditions and supplying biotin. Within such expanded niches, lignocellulose degradation proceeds sequentially, and the availability of breakdown products to E. coli is constrained by two interlinked processes. Specifically, Lachnoclostridium sp. produces oligosaccharides that are largely inaccessible to E. coli. A subset of these oligosaccharides is utilized by C. beijerinckii to produce monosaccharides that support E. coli growth, while glycosidase secretion by C. beijerinckii is reduced under coculture conditions. Building on these findings, we designed a synthetic consortium by coculturing C. beijerinckii with an engineered E. coli strain that expresses xylanase genes from an unculturable Lachnoclostridium. This consortium achieved isopropanol production from hemicellulose without requiring anaerobic conditions. Our findings reveal the niche-expanding role of nondegraders and the processes that constrain their access to degradation products, offering insights into maintaining stable cooperation in biopolymer-degrading communities and designing efficient consortia for biopolymer conversion.
    Keywords:  biopolymer degradation; exploitation alleviation; mutualistic interaction; niche expansion; nondegrader
    DOI:  https://doi.org/10.1073/pnas.2500664122
  12. Nature. 2025 Jul 23.
    Mechanical underwater adhesive devices for soft substrates.
    Ziliang Kang, Johanna A Gomez, Alisa MeiShan Ross, Ameya R Kirtane, Ming Zhao, Yubin Cai, Fu Xing Chen, Corona L Chen, Isaac Diaz Becdach, Rajib Dey, Andrei Russel Ismael, Injoo Moon, Yiyuan Yang, Benjamin N Muller, Mehmet Girayhan Say, Andrew Pettinari, Jason Kobrin, Joshua Morimoto, Ted Smierciak, Aaron Lopes, Ayten Ebru Erdogan, Matt Murphy, Niora Fabian, Ashley Guevara, Benedict Laidlaw, Kailyn Schmidt, Alison M Hayward, Alexandra H Techet, Christopher P Kenaley, Giovanni Traverso.
      Achieving long-term underwater adhesion to dynamic, regenerating soft substrates that undergo extreme fluctuations in pH and moisture remains a major unresolved challenge, with far-reaching implications for healthcare, manufacturing, robotics and marine applications1-16. Here, inspired by remoras-fish equipped with specialized adhesive discs-we developed the Mechanical Underwater Soft Adhesion System (MUSAS). Through detailed anatomical, behavioural, physical and biomimetic investigations of remora adhesion on soft substrates, we uncovered the key physical principles and evolutionary adaptations underlying their robust attachment. These insights guided the design of MUSAS, which shows extraordinary versatility, adhering securely to a wide range of soft substrates with varying roughness, stiffness and structural integrity. MUSAS achieves an adhesion-force-to-weight ratio of up to 1,391-fold and maintains performance under extreme pH and moisture conditions. We demonstrate its utility across highly translational models, including in vitro, ex vivo and in vivo settings, enabling applications such as ultraminiaturized aquatic kinetic temperature sensors, non-invasive gastroesophageal reflux monitoring, long-acting antiretroviral drug delivery and messenger RNA administration via the gastrointestinal tract.
    DOI:  https://doi.org/10.1038/s41586-025-09304-4
  13. Adv Colloid Interface Sci. 2025 Jul 15. pii: S0001-8686(25)00213-1. [Epub ahead of print]344 103602
    3D printing of hydrogel nanocomposites: A symbiotic union for advanced biomedical applications.
    Nariman Rajabifar, Mohammad Hesam Alemi, Amir Rostami, Payam Zarrintaj, Yasser Zare, Muhammad Tajammal Munir, Mohsen Shahrousvand, Kyong Yop Rhee, Hossein Nazockdast.
      Hydrogels have emerged as thriving materials for developing biomedical devices due to their biocompatibility and hydrophilic nature, encompassing various fields from biomedical engineering and pharmaceuticals to wound care and tissue scaffolding. Nevertheless, traditional hydrogels are beset with poor mechanical strength, limited controlled release of medicines, and irreversible chain breakage, all of which compromise their efficacy in practice. The desirable performance of hydrogels can be notably lifted upon incorporating nanomaterials, yielding tunable functions for devising next-generation biocompatible structures. Despite the alluring prospects offered by hydrogel nanocomposites, the processing of these materials is still in its infancy and remains full of challenges to produce personalized, tangible items. Herein, we endeavor to bridge the gap between hydrogel nanocomposites for biomedical applications with additive manufacturing processing, providing a useful guideline for comparing and selecting viable three-dimensional (3D) printing approaches. We review the background of synthesizing hydrogel nanocomposites along with the key concepts toward biomedical applications, featuring a survey on the recent reports on 3D printing of hydrogel nanocomposites for developing customized tissues, drug delivery, bioadhesives, wound dressing, and biosensors.
    Keywords:  Additive manufacturing; Advanced materials; Drug delivery hydrogels; Nanocomposite hydrogels; Tissue engineering
    DOI:  https://doi.org/10.1016/j.cis.2025.103602
  14. Nat Biomed Eng. 2025 Jul 18.
    Mannich reaction-based combinatorial libraries identify antioxidant ionizable lipids for mRNA delivery with reduced immunogenicity.
    Ningqiang Gong, Dongyoon Kim, Mohamad-Gabriel Alameh, Rakan El-Mayta, Emily L Han, Garima Dwivedi, Rohan Palanki, Qiangqiang Shi, Xuexiang Han, Lulu Xue, Junchao Xu, Zilin Meng, Tianyu Luo, Christian G Figueroa-Espada, Drew Weissman, Jinghong Li, Michael J Mitchell.
      The immunogenicity of lipid nanoparticles (LNPs) used for the delivery of nucleoside-modified messenger RNA limits the levels and durability of expression of the encoded protein. Here, by leveraging the Mannich reaction for ionizable lipid synthesis, and via the in vitro and in vivo screening of six combinatorial libraries of synthesized lipids, we report the identification of an antioxidant ionizable lipid, C-a16, exhibiting reduced immunogenicity. When incorporated into LNPs for mRNA delivery, C-a16 mitigated the generation of intracellular reactive oxygen species, thereby extending the duration of protein expression. In mice, and compared with commercial LNPs, LNPs incorporating C-a16 and co-delivering Cas9 mRNA and guide RNA for the editing of the transthyretin gene led to 2.8-fold higher editing efficiency; LNPs with C-a16 delivering fibroblast growth factor 21 mRNA increased the expression of the protein 3.6-fold; and when delivering mRNA encoding a tumour neoantigen or the spike protein of SARS-CoV-2, LNPs with C-a16 induced stronger antigen-specific immune responses. Our findings support the further testing of C-a16 as a promising ionizable lipid for mRNA delivery in therapeutic applications.
    DOI:  https://doi.org/10.1038/s41551-025-01422-8
  15. N Biotechnol. 2025 Jul 17. pii: S1871-6784(25)00071-8. [Epub ahead of print]89 105-118
    Conditional guide RNA deactivation by mRNA and small molecule triggers in Saccharomyces cerevisiae.
    Chenggang Xi, Stephen Chiu, William E Voje, James M Carothers, Tae Seok Moon.
      CRISPR interference (CRISPRi) technologies have revolutionized bioengineering by providing precise tools for gene expression modulation, enabling targeted gene perturbation and metabolic pathway optimization. Despite these advances, achieving dynamic control over gene expression by CRISPR-based regulation remains a challenge due to its inherently static nature. Utilizing toehold-mediated strand displacement and ligand-responsive ribozymes (aptazymes), this study introduces switchable guide RNAs (gRNAs) that facilitate tunable gene expression mediated by mRNA or small molecule signals. We demonstrate complete silencing of gRNA via strategically designed 5' or 3' extensions that impede the gRNA spacer or the dCas9 handle, with subsequent restoration of function through sequestration or cleavage of the obstructive sequence. The resulting toehold-embedded or aptazyme-embedded gRNAs can be deactivated by specific signals, including two full-length translatable mRNAs and two small molecule triggers, thereby lifting CRISPRi repression on targeted genes. This modular approach allows for gRNA-based biocomputing through multi-layer or multi-input genetic logic gates in Saccharomyces cerevisiae. Offering a versatile strategy for post-CRISPR regulation in response to environmental signals or cellular states, this methodology expands the toolkit in eukaryotic systems for reversible control of gene expression.
    Keywords:  Aptazyme; CRISPRi; Genetically encoded biosensor; Guide RNA switch; Toehold-mediated strand displacement; mRNA detection
    DOI:  https://doi.org/10.1016/j.nbt.2025.07.004
  16. ACS Synth Biol. 2025 Jul 21.
    Hydrogel-Immobilized Multienzyme Systems for Cell-Free Chemical Bioproduction.
    Widianti Sugianto, Ryan A L Cardiff, Claire Benstead, Gokce Altin-Yavuzarslan, Lilo Pozzo, Alshakim Nelson, James M Carothers.
      Cell-free gene expression systems derived from bacterial lysates enable the expression of biosynthetic pathways from inexpensive and easily prepared DNA templates. These systems hold great promise for modular and on-demand bioproduction of valuable small molecules in resource-limited settings but are constrained in their long-term stability, reusability, and deployability. In this work, we demonstrate that multiple cell-free expressed enzymes can be co-immobilized in biocompatible hydrogels made from poly(ethylene glycol) diacrylate (PEGDA) with added glycerol for enhanced gel integrity. Using small-angle X-ray scattering (SAXS), we show that the mesh size of PEGDA-glycerol hydrogels is comparable to the globular sizes of many proteins and enzymes, which could be used for protein entrapment. We found that the combination between entrapment and chemical ligation of the enzymes was effective to retain proteins. By employing a method for direct fluorescence measurement from hydrogels, we found that proteins can be retained in PEGDA-glycerol for at least a week. By separating the cell-free enzyme expression from the immobilization step, we successfully fabricated enzyme-laden hydrogels with three heterologous cell-free enzymes for the bioconversion of pyruvic acid to malic acid, an industrially valuable and versatile precursor chemical. Both heterologous and endogenous enzymes from the lysate remain functional in photo-cross-linked hydrogels and can be reused for multiple biocatalytic cycles. Moreover, we also found that the immobilized enzymes exhibit up to 1.6-fold higher activity and 2-fold longer lifetimes than free enzymes in liquid reactions. These results could advance the deployment of cell-free synthetic biology because they show that reusable, stable, and durable multienzyme systems can be created using readily available materials and fabrication techniques.
    Keywords:  cell-free bioproduction; cell-free systems; enzyme immobilization; enzyme-laden hydrogels; multienzyme systems; reusable biocatalysts
    DOI:  https://doi.org/10.1021/acssynbio.5c00234
  17. Gut Microbes. 2025 Dec;17(1): 2534673
    Genome-scale metabolic modelling of human gut microbes to inform rational community design.
    Juan Pablo Molina Ortiz, Dale David McClure, Andrew Holmes, Scott Alan Rice, Mark Norman Read, Erin Rose Shanahan.
      The human gut microbiome impacts host health through metabolite production, notably short-chain fatty acids (SCFAs) derived from digestion-resistant carbohydrates (DRCs). While DRC supplementation offers a means to modulate the microbiome therapeutically, its effectiveness is often limited by the microbial community's complexity and individual variability in microbiome functionality. We utilized genome-scale metabolic models (GEMs) from the AGORA collection to provide a system-level overview of the metabolic capabilities of human gut microbes in terms of carbohydrate trophic networks and propose improved therapeutic interventions, based on microbial community design. Our study inferred the capability of AGORA strains to consume carbohydrates of varying structural complexities - including DRCs - and to produce metabolites amenable to cross-feeding, such as SCFAs. The resulting functional database indicated that DRC-degrading abilities are rare among gut microbes, suggesting that the presence or absence of specific taxa can determine the success of DRC-based interventions. Additionally, we found that metabolite production profiles exceed family-level variation, highlighting the limitations in predicting intervention outcomes based on gut microbial composition assessed at higher taxonomic levels. In response to these findings, we integrate reverse ecology principles, network analysis and GEM community modeling to guide the design of minimal yet resilient microbial communities to better guarantee intervention response (purpose-based communities). As a proof of principle, we predicted a purpose-based community designed to enhance butyrate production when used in conjunction with DRC supplementation that displays resilience under nutritional stress, such as amino acid restriction. We further seeded the identified purpose-based community into modeled human microbiomes previously demonstrated to accurately predict SCFA production profiles. The analysis confirmed that such intervention significantly promotes butyrate production across samples, with those that presented a comparatively lower butyrate production pre-intervention displaying the largest increase in butyrate production after seeding. Our work highlights the potential of combining GEMs with community design to infer effective microbiome interventions, ultimately leading to improved health outcomes.
    Keywords:  GEMs; Gut microbiome; community design; consortia design; genome scale metabolic modeling; human; intervention design; metabolic network modeling; reverse ecology
    DOI:  https://doi.org/10.1080/19490976.2025.2534673
  18. J Am Chem Soc. 2025 Jul 23.
    Dynamic Modulation of Multicellular Interactions via ATP-Dissipative DNA Assembly.
    Yi Xu, Yao Luo, Xiaoyun Lu, Jingyi Ye, Zeyu Chen, Yao Hu, Chen Shen, Bin Zhao, Erfeng Kou, Jie Deng, Chunhai Fan, Huan Zhang, Honglu Zhang.
      Living cells exhibit dynamic adaptability through ATP-fueled processes that are crucial for tissue development and immune responses. Conventional methods for controlling cell assembly lack the nonequilibrium, reversible behavior of natural systems. Here, we present an ATP-dissipative DNA assembly system that leverages DNA's programmability to enable adaptive, hierarchical structures with spatiotemporal control. By utilizing various DNA monomers, including double-stranded DNA (dsDNA), tetrahedral DNA frameworks, and branched DNA frameworks, we achieve the precise regulation of cell assembly in response to ATP-driven enzymatic reactions. BDF-based condensates, formed through multivalent liquid-liquid phase separation (LLPS), dynamically modulate intercellular interactions, mimicking the extracellular matrix adaptability. This system was successfully applied to regulate cell assembly in Ramos, PC-12, and natural killer (NK) cells. By harnessing endogenous ATP secreted by cells, we enabled real-time reversible control over cell assembly. Furthermore, the ATP-dissipative assembly system enhanced the tumor-killing efficacy of NK cells by modulating their interactions with cancer cells. This work highlights the potential of DNA-based dissipative self-assembly for precise spatiotemporal regulation of cellular interactions, shedding light on advanced applications in intelligent materials and immunotherapy.
    DOI:  https://doi.org/10.1021/jacs.5c08925
  19. Nat Commun. 2025 Jul 19. 16(1): 6672
    Deciphering the assembly process of PQQ dependent methanol dehydrogenase.
    Haichuan Zhou, Junqing Sun, Jian Cheng, Min Wu, Jie Bai, Qian Li, Jie Shen, Manman Han, Chen Yang, Liangpo Li, Yuwan Liu, Qichen Cao, Weidong Liu, Haixia Xiao, Hongjun Dong, Feng Gao, Huifeng Jiang.
      Pyrroloquinoline quinone (PQQ)-dependent methanol dehydrogenases (MDHs), the periplasmic metalloenzymes in Gram-negative methylotrophic bacteria, play a pivotal role in methane and methanol bio-utilization. Although the structures of many PQQ-dependent MDHs have been resolved, including the canonical heterotetrameric enzymes composed of two MxaF and two MxaI subunits with a molecule of PQQ and a calcium ion in the active site in MxaF, the biogenesis of these enzymes remains elusive. Here, we characterize a chaperone, MxaJ, responsible for PQQ incorporation by reconstructing a PQQ-dependent MDH assembly system in Escherichia coli. Using cryo-electron microscopy, we capture the structures of the intermediate complexes formed by the chaperone MxaJ and catalytic subunit MxaF during PQQ-dependent MDH maturation, revealing a chaperone-mediated molecular mechanism of cofactor incorporation. These findings not only advance our understanding on the biogenesis of PQQ-dependent MDH, but also provide an alternative engineering way for methane and methanol bioconversion.
    DOI:  https://doi.org/10.1038/s41467-025-61958-w
  20. Adv Mater. 2025 Jul 21. e08265
    Visible Light-Driven Spatiotemporal-Resolved Proton Management by Harnessing Merocyanine-Integrated Hydrogels as Regenerative Photoacid Matrices.
    Guodong Wang, Meiqing Yang, Ze Gong, Chuang Li.
      Photomanipulation of the environmental pH plays a crucial role in modulating the reaction kinetics and engineering material functionalities. While conventional merocyanine photoacids offer pH modulability, their practical implementation is fundamentally constrained by aqueous dissolution and laborious regeneration. Here, a transformative strategy is reported through the covalent integration of merocyanine photoacids into hydrophilic polymer networks to construct regenerative photoacid matrices, which stably retain protons in the dark and spatiotemporally liberate them upon illumination. The photoacid matrix overcomes solubility constraints through adjustable merocyanine grafting density while simultaneously enhancing alkaline stability, thereby enabling shape-governed, diffusion-controlled proton release kinetics. The universality of this approach has been extensively verified in multiple polymer matrices with variable chemical compositions. Upon straightforward separation and acidic regeneration in the dark, the recovered matrices sustainably maintain robust photoactivated proton release capability. This not only enables programmable control over acid-base indicator discoloration but also guides hierarchical self-assembly of arylazopyrazole-based hydrogelators, yielding 3D supramolecular gel architectures with tailored complexity. Furthermore, spatially controlled directional proton liberation are established through synergistically addressing negative phototropic deformation within a low-density crosslinked photoacid matrix. This work creates a new paradigm for spatiotemporal pH manipulation in the development of autonomous materials through regenerative photoacid matrices.
    Keywords:  arylazopyrazole; hydrogel; merocyanine; photoacid; regeneration
    DOI:  https://doi.org/10.1002/adma.202508265
  21. Adv Colloid Interface Sci. 2025 Jul 14. pii: S0001-8686(25)00206-4. [Epub ahead of print]344 103595
    Polysaccharide-based nanoparticles for 3D (bio)printing.
    Zahra Khorsandi, Mehdi Maham, Valiollah Mirkhani, Benjamin Kruppke, Hossein Ali Khonakdar.
      Biopolymers are known as environmental materials with massive applications in various fields. Among biopolymers, polysaccharides are bioactive, renewable, bioresorbable, biocompatible, biodegradable, and hydrophilic. These brilliant properties have made them promising materials for use in emerging technologies. Three-dimensional (3D) printing of these green materials has extensive applications in clinical usage, novel electronic devices, developed resin and polymers, absorbents, etc. This review describes the recent development of employing polysaccharide-based nanomaterials in the construction of different bio-products by using extrusion, laser, inkjet 3D printing, and vat polymerization methods. The influence of incorporating nanoparticles (NPs) on the properties of the final 3D-printed composite comprising reinforcement effects, mechanical properties, viscosity, printability, shear-thinning property, biocompatibility, structural integrity, and interactions have been evaluated. This review helps researchers keep up with developments in polysaccharide-based 3D-printed composites, with the vision that NPs can potentially revolutionize the bioink issue in the future.
    Keywords:  3D (bio)printing; Biomaterials; Biomimetic scaffolds; Nanoparticles; Polysaccharides
    DOI:  https://doi.org/10.1016/j.cis.2025.103595
  22. ACS Synth Biol. 2025 Jul 23.
    Engineering Cell Fate with Adaptive Feedback Control.
    Frank Britto Bisso, Giulia Giordano, Christian Cuba Samaniego.
      Engineering cell fate is fundamental to optimizing therapies based on stem cells, which are aimed at replacing cells in patients suffering from trauma or disease. By timely administering molecular regulators (e.g., transcription factors, RNAs, or small molecules) in a process that mimics in vivo embryonic development, stem cell differentiation can be guided toward a specific cell fate. However, scaling up these therapies is extremely challenging because such differentiation strategies often result in mixed cellular populations. While synthetic biology approaches have been proposed to increase the yield of desired cell types, designing gene circuits that effectively redirect cell fate decisions requires mechanistic insight into the dynamics of the endogenous regulatory networks that govern this type of decision-making. In this work, we present a biomolecular adaptive controller designed to favor a specific cell fate. The controller, whose topology is akin to that of an Incoherent Feedforward Loop (IFFL), requires minimal knowledge of the endogenous network as it exhibits adaptive, non-reference-based behavior. The synthetic circuit operates through a sequestration mechanism and a delay introduced by an intermediate species, producing an output that asymptotically approximates a discrete temporal derivative of its input if the sequestration rate is sufficiently fast. Allowing the controller to actuate over a target species involved in the decision-making process creates a tunable synthetic bias that favors the production of the desired species with minimal alteration to the overall equilibrium landscape of the endogenous network. Through theoretical and computational analysis, we provide design guidelines for the controller's optimal operation, evaluate its performance under parametric perturbations, and extend its applicability to various examples of common multistable systems in biology.
    Keywords:  adaptive control; cell fate; feedback control; genetic circuits; incoherent feedforward loop; multistability
    DOI:  https://doi.org/10.1021/acssynbio.5c00299
  23. ACS Appl Mater Interfaces. 2025 Jul 22.
    Scalable Biofabrication of Functional 3D Scaffolds via Synergy of Autopilot Single-Jet Electrospun 3D PCL Fiber Scaffolds and Cell-Laden Hydrogels.
    Balchandar Navaneethan, Mehdi Salar Amoli, Yen-Ching Yang, Sarah Rezapourdamanab, Chiao-Yu Tseng, Yamini Singh, Chin-Lin Guo, Vahid Serpooshan, Chia-Fu Chou.
      3D bioprinting enables cell-laden hydrogel construct fabrication in a layer-by-layer fashion but faces scalability challenges due to the mechanical weakness of hydrogels. Matrix reinforcement compromises cellular activity, creating a scalability-functionality trade-off that remains unresolved as sophisticated strategies including sequential and embedded printing fail to effectively overcome these limitations. This study presents an alternative approach by integrating autopilot single-jet electrospun (AJ-3D ES) 3D PCL fiber scaffolds with hydrogels, achieving anatomical precision, mechanical robustness, and enhanced cell function. Hydrogel dip-coating of anatomically structured PCL scaffolds enabled organ-scale cellular constructs. By providing an ECM-mimicking porous fiber network, embedded cells mitigated the limitations of hydrogel stiffness (even ∼50 kPa) and facilitated cell-cell interactions, supporting epithelialization, fibroblast clustering, and 3D phase-separated HepG2-HUVEC co-cultures. Contour 3D bioprinting along PCL fiber scaffold topographies facilitated endothelial patterning for vascularization and native-tissue mimicking complexity. Volumetric scalability was demonstrated through hydrogel casting, embedded bioprinting, and modular stacking within 3D PCL fiber scaffolds, ensuring hydrogel integrity while maintaining medium diffusion for sustained cell survival and function. In vivo studies confirmed the proangiogenic nature of PCL fiber scaffolds with tissue bridging via cell infiltration and ECM collagen deposition, underscoring clinical translational potential. By integrating topographic and volumetric flexibility, this approach advances biofabrication strategies for functional tissue and organ constructs.
    Keywords:  3D bioprinting; Biofabrication; PCL fiber; cell-laden hydrogels; electrospinning; functional constructs
    DOI:  https://doi.org/10.1021/acsami.5c07425
  24. Nat Commun. 2025 Jul 22. 16(1): 6690
    Docking domains from modular polyketide synthases and their use in engineering.
    Sabrina Collin, Kira J Weissman.
      
    DOI:  https://doi.org/10.1038/s41467-025-61435-4
  25. Nat Commun. 2025 Jul 23. 16(1): 6802
    Dynamic control of ferroic domain patterns by thermal quenching.
    Jan Gerrit Horstmann, Ehsan Hassanpour, Aaron Merlin Müller, Yannik Zemp, Thomas Lottermoser, Yusuke Tokunaga, Yasujiro Taguchi, Yoshinori Tokura, Mads C Weber, Manfred Fiebig.
      Controlling domain structures in ferroic materials is key to manipulating their functionality. Typically, quasi-static electric or magnetic fields are used to transform ferroic domains. In contrast, metallurgy employs rapid thermal quenches across phase transitions to create new domain patterns. This nonequilibrium approach overcomes constraints imposed by slow interactions, yet remains largely unexplored in ferroics. Here, we use thermal quenches to control ferroic domain patterns in a rare-earth orthoferrite. Cooling at variable rates triggers transitions between two ferroic phases, with transient domain evolution enabling selection of the final domain pattern. By tuning the quench rate, we either obtain the intrinsic domain structure of the low-temperature phase or transfer the high-temperature pattern-creating a hidden metastable domain state inaccessible at thermal equilibrium. Real-time imaging during quenching reveals two timescales: fast domain fragmentation followed by slower relaxation. This dynamic control of domain configurations offers a promising approach for manipulating ferroic order.
    DOI:  https://doi.org/10.1038/s41467-025-62158-2
  26. Nat Biomed Eng. 2025 Jul 18.
    Precise virulence inactivation using a CRISPR-associated transposase for combating Enterobacteriaceae gut pathogens.
    Carlotta Ronda, Tyler Perdue, Logan Schwanz, Diego Rivera Gelsinger, Leonie Brockmann, Andrew Kaufman, Yiming Huang, Samuel H Sternberg, Harris H Wang.
      Targeted gene manipulation in a complex microbial community is an enabling technology for precise microbiome editing. Here we introduce BACTRINS, an in situ microbiome engineering platform designed for efficient and precise genomic insertion of a desired payload and simultaneous knockout of target genes. This system leverages conjugation-mediated delivery of CRISPR-associated transposases to achieve RNA-guided genomic integration, allowing precise insertion of a therapeutic payload while neutralizing pathogen virulence without causing cell death. When applied against an Enterobacteriaceae Shiga toxin-producing pathogen in the gut, this system delivers a CRISPR-associated transposase by bacterial conjugation for site-specific inactivation of the Shiga toxin gene and integration of a nanobody therapeutic payload to disrupt pathogen attachment. A single dose of this therapy results in high-efficiency Shiga gene inactivation and improved survival in a murine infection model of Shiga-producing pathogen. This work establishes a new type of live bacterial therapeutic capable of reducing gut infections by transforming toxigenic pathogens into commensal protectors.
    DOI:  https://doi.org/10.1038/s41551-025-01453-1
  27. Macromol Res. 2025 ;33(7): 921-931
    Ionically crosslinked biohybrid gelatin-based hydrogels for 3D cell culture.
    Eric Y Du, H T Kim Duong, M A Kristine Tolentino, Jacinta L Houng, Panthipa Suwannakot, Kristel C Tjandra, Duyen H T Nguyen, Richard D Tilley, J Justin Gooding.
      The transition from two-dimensional to three-dimensional cell cultures has transformed the understanding of cell physiology and cell-matrix interactions. Extracellular matrix (ECM) mimics tend to fall into either the natural or synthetic categories. Naturally occurring ECM mimics, such as collagen and gelatin, have superior bioactive properties but typically lack tuneability. Conversely, synthetic ECM mimics are highly defined but even with modifications, can lack the bioactivity of natural proteins. Therefore, to take advantage of the potential of both natural and synthetic ECM mimics, a biohybrid ionically crosslinked gelatin hydrogel was synthesised. This was achieved by utilising free amine groups along the gelatin backbone as the basis for a reversible addition - fragmentation chain-transfer (RAFT) reaction. The resulting polymers had tuneable stiffness and enhanced solubility compared to gelatin. The biohybrid gel also showed good biocompatibility, with MCF-7 cells forming larger spheroids when encapsulated within the biohybrid gel when compared to an unfunctionalized polyethylene-glycol (PEG) gel. Furthermore, due to the ionic crosslinking in the biohybrid gel, spheroids can be retrieved by digesting the matrix using 10 × phosphate-buffered saline (PBS). Retrieved cells were shown to be viable which allows for the potential of downstream analysis. Thus, this study highlights the potential of hybrid gelatin-PEG hydrogels for 3D cell culture.
    Graphical abstract: The biohybrid gelatin (Gelatin-SPMA) is crosslinked with a positively charged polymer (PEG-MAETMA) to form a gel within seconds. MCF-7 cells survived encapsulation and formed spheroids over 7 days. 10x phosphate buffered saline (PBS) was then used to digest the hydrogel, allowing for the recovery of encapsulated spheroids.
    Supplementary Information: The online version contains supplementary material available at 10.1007/s13233-025-00380-z.
    Keywords:  ECM mimic; Gelatin; Hydrogel; Polymer
    DOI:  https://doi.org/10.1007/s13233-025-00380-z
  28. ACS Synth Biol. 2025 Jul 22.
    Systematic Mapping of Bacterial CRISPRa Systems for Synergistic Gene Activation Reveals Antagonistic Effects.
    Cholpisit Kiattisewee, Ava V Karanjia, Ryan A L Cardiff, Kira E Olander, Pansa Leejareon, Sarah S Alvi, James M Carothers, Jesse G Zalatan.
      CRISPR gene activation (CRISPRa) tools have shown great promise for bacterial strain engineering but often require customization for each intended application. Our goal is to create generalizable CRISPRa tools that can overcome previous limitations of gene activation in bacteria. In eukaryotic cells, multiple activators can be combined for synergistic gene activation. To identify potential effectors for synergistic activation in bacteria, we systematically characterized bacterial activator proteins with a set of engineered synthetic promoters. We found that optimal target sites for different activators could vary by up to 200 bases in the region upstream of the transcription start site (TSS). These optimal target sites qualitatively matched previous reports for each activator, but the precise targeting rules varied between different promoters. By characterizing targeting rules in the same promoter context, we were able to test activator combinations with each effector positioned at its optimal target site. We did not find any activator combinations that produced synergistic activation, and we found that many combinations were antagonistic. This systematic investigation highlights fundamental mechanistic differences between bacterial and eukaryotic transcriptional activation systems and suggests that alternative strategies will be necessary for strong bacterial gene activation at arbitrary endogenous targets.
    Keywords:  CRISPR activation; bacterial CRISPRa; bacterial gene activation; synergistic activation
    DOI:  https://doi.org/10.1021/acssynbio.5c00358
  29. Nat Commun. 2025 Jul 24. 16(1): 6831
    Unveiling the hidden interactome of CRBN molecular glues.
    Kheewoong Baek, Rebecca J Metivier, Shourya S Roy Burman, Jonathan W Bushman, Hojong Yoon, Ryan J Lumpkin, Julia K Ryan, Dinah M Abeja, Megha Lakshminarayan, Hong Yue, Samuel Ojeda, Yuan Xiong, Jianwei Che, Alyssa L Verano, Anna M Schmoker, Nathanael S Gray, Katherine A Donovan, Eric S Fischer.
      Induced proximity by molecular glues refers to strategies that leverage the recruitment of proteins to facilitate their modification, regulation or degradation. As prospective design of molecular glues remains challenging, unbiased discovery methods are necessary to discover new chemical targets. Here we establish a high throughput affinity proteomics workflow leveraging E3 ligase activity-impaired CRBN-DDB1ΔB in cell lysates for the unbiased identification of molecular glue targets. By mapping the interaction landscape of CRBN-binding molecular glues, we unveil 298 protein targets and demonstrate the utility of enrichment methods for identifying targets overlooked by established methods. We use a computational workflow to estimate target confidence and perform biochemical and structural validation of uncharacterized neo-substrates. We further identify a lead compound for the previously untargeted non-zinc finger PPIL4 through a biochemical screen. Our study provides a comprehensive inventory of targets chemically recruited to CRBN and delivers a robust and scalable workflow for identifying drug-induced protein interactions in cell lysates.
    DOI:  https://doi.org/10.1038/s41467-025-62099-w
  30. Nucleic Acids Res. 2025 Jul 19. pii: gkaf703. [Epub ahead of print]53(14):
    Genetic "expiry-date" circuits control lifespan of synthetic scavenger bacteria for safe bioremediation.
    Kha Mong Tran, Nuong Thi Nong, Jun Ren, Kangseok Lee, Doheon Lee, Jörg Gsponer, Hyang-Mi Lee, Dokyun Na.
      Synthetic biology enabled the systematic engineering of bacteria for diverse applications, but their deployment in open environments raises concerns about their persistence and unintended ecological impacts. To address these challenges, genetic "expiry-date" circuits were designed to impose a tunable lifespan on bacteria. These circuits, structured as a feedforward activation network, regulate the timing of cell death by controlling the expression of Lysis E, enabling a programmed lifespan ranging from hours to days. The lifespan can be tailored by modifying the number of activation steps in the cascade. The circuits were optimized by reducing gene expression leakiness of Lysis E using a synthetic small regulatory RNA and combining it with an asd-based auxotrophic system. The bacteria harboring the "expiry-date" circuits resulted in a GMO escape rate below U.S. NIH release standards (<10-10). To validate the practical applicability of this system, a synthetic phenol-scavenging Escherichia coli was constructed, which possessed enhanced phenol tolerance and phenol-detoxification capability, and harbored the "expiry-date" circuits. The engineered bacteria detoxified 0.1 g/kg of phenol in soil within 4 days and self-destructed by day 5. These results support the circuit's potential as a biocontainment strategy for the safe and controlled deployment of synthetic bacteria in real-world applications.
    DOI:  https://doi.org/10.1093/nar/gkaf703
  31. Nat Commun. 2025 Jul 18. 16(1): 6637
    Engineering glycosyltransferases into glycan binding proteins using a mammalian surface display platform.
    Ryoma Hombu, Lauren E Beatty, John Tomaszewski, Sheldon Park, Sriram Neelamegham.
      Traditional lectins exhibit broad binding specificity for cell-surface carbohydrates, and generating anti-glycan antibodies is challenging due to low immunogenicity. Nevertheless, it is necessary to develop glycan binding proteins for single-cell glycosylation pathway analysis. Here, we test the hypothesis that protein engineering of mammalian glycosyltransferases can yield glycan-binding proteins with defined specificity. Introducing an H302A mutation, based on rational design, into porcine ST3Gal1 abolishes its enzymatic activity, but results in a lectin that specifically binds sialylated core-2 O-linked glycans (Neu5Acα2-3Galβ1-3[GlcNAc(β1-6)]GalNAcα). To improve binding, we develop a mammalian cell-surface display platform to screen variants. One ST3Gal1 mutant (sCore2) with three mutations, H302A/A312I/F313S exhibits enhanced binding specificity. Spectral flow cytometry and tissue microarray analysis using sCore2 reveal distinct cell- and tissue-specific sialyl core-2 staining patterns in human blood cells and paraffin-embedded tissue sections. Overall, glycosyltransferases can be engineered to generate specific glycan binding proteins, suggesting that a similar approach may be extended to other glycoenzymes.
    DOI:  https://doi.org/10.1038/s41467-025-62018-z
  32. Biofabrication. 2025 Jul 23.
    Engineering a microfluidic-assisted 3D bioprinting approach for the hierarchical control deposition and compartmentalisation of graded bioinks.
    Federico Serpe, Lucia Iafrate, Marco Bastioli, Martina Marcotulli, Caterina Sanchini, Valeria De Turris, Michele D'Orazio, Biagio Palmisano, Arianna Mencattini, Eugenio Martinelli, Mara Riminucci, Carlo Massimo Casciola, Giancarlo Ruocco, Chiara Scognamiglio, Gianluca Cidonio.
      The advent of 3D bioprinting has revolutionised tissue engineering and regenerative medicine (TERM). Today, tissues of single cell type can be fabricated with extreme resolution and printing fidelity. However, the ultimate functionality of the desired tissue is limited, due to the absence of a multicellular population and diversity in micro-environment distribution. Currently, 3D bioprinting technologies are facing challenges in delivering multiple cells and biomaterials in a controlled fashion. The use of interchangeable syringe-based systems has often favoured the delamination between interfaces, greatly limiting the fabrication of interconnected tissue constructs. Microfluidic-assisted 3D bioprinting platforms have been found capable of rescuing the fabrication of tissue interfaces, but often fails to guarantee printing fidelity, cell density control and compartmentalisation. Herein, we present the convergence of microfluidic and 3D bioprinting platforms into a deposition system capable of harnessing a microfluidic printhead for the continuous rapid fabrication of interconnected functional tissues. The use of flow-focusing and passive mixer printhead modules allowed for the rapid and dynamic modulation of fibre diameter and material composition, respectively. Cells were compartmentalised into discrete three-dimensional layers with defined density patterns, confirming the punctual control of the presented microfluidic platform in arranging cells and materials in 3D. In ovo and in vivo studies demonstrated the seminal functionality of 3D bioprinted constructs with patterned vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1), respectively. This, in turn, facilitated the simulation of diverse cellular environments and proliferation pathways within a single construct, which is currently unachievable with conventional 3D bioprinting techniques, offering new opportunities for the fabrication of functionally graded systems and physiologically-relevant skeletal tissue substitutes.
    Keywords:  bioprinting; bone; cell patterns; gradient; microfluidics; tissue engineering
    DOI:  https://doi.org/10.1088/1758-5090/adf35b
  33. PLoS Comput Biol. 2025 Jul 21. 21(7): e1013296
    A modular model integrating metabolism, growth, and cell cycle predicts that fermentation is required to modulate cell size in yeast populations.
    Marco Vanoni, Pasquale Palumbo, Federico Papa, Stefano Busti, Laura Gotti, Meike Wortel, Bas Teusink, Ivan Orlandi, Alex Pessina, Cristina Airoldi, Luca Brambilla, Marina Vai, Lilia Alberghina.
      For unicellular organisms, the reproduction rate and growth are crucial fitness determinants and functional manifestations of the organism genotype. Using the budding yeast Saccharomyces cerevisiae as a model organism, we integrated metabolism, which provides energy and building blocks for growth, with cell mass growth and cell cycle progression into a low-granularity, multiscale (from cell to population) computational model. This model predicted that cells with constitutive respiration do not modulate cell size according to the growth conditions. We experimentally validated the model predictions using mutants with defects in the upper part of glycolysis or glucose transport. Plugging in molecular details of cellular subsystems allowed us to refine predictions from the cellular to the molecular level. Our hybrid multiscale modeling approach provides a framework for structuring molecular knowledge and predicting cell phenotypes under various genetic and environmental conditions.
    DOI:  https://doi.org/10.1371/journal.pcbi.1013296
  34. Proc Natl Acad Sci U S A. 2025 Jul 29. 122(30): e2425319122
    Leveraging chromatin packing domains to target chemoevasion in vivo.
    Jane Frederick, Ranya K A Virk, I Chae Ye, Luay M Almassalha, Greta M Wodarcyk, David VanDerway, Ruyi Gong, Cody L Dunton, Tiffany Kuo, Karla I Medina, Margarita Loxas, Jared T Ahrendsen, Demirkan B Gursel, Paola Carrillo Gonzalez, Rikkert J Nap, Saira John, Vasundhara Agrawal, Nicholas M Anthony, John Carinato, Wing Shun Li, Rivaan Kakkaramadam, Surbhi Jain, Shohreh Shahabi, Guillermo A Ameer, Igal G Szleifer, Vadim Backman.
      Cancer cells exhibit a remarkable resilience to cytotoxic stress, often adapting through transcriptional changes linked to alterations in chromatin structure. In several types of cancer, these adaptations involve epigenetic modifications and restructuring of topologically associating domains. However, the underlying principles by which chromatin architecture facilitates such adaptability across different cancers remain poorly understood. To investigate the role of chromatin in this process, we developed a physics-based model that connects chromatin organization to cell fate decisions, such as survival following chemotherapy. Our model builds on the observation that chromatin forms packing domains, which influence transcriptional activity through macromolecular crowding. The model accurately predicts chemoevasion in vitro, suggesting that changes in packing domains affect the likelihood of survival. Consistent results across diverse cancer types indicate that the model captures fundamental principles of chromatin-mediated adaptation, independent of the specific cancer or chemotherapy mechanisms involved. Based on these insights, we hypothesized that compounds capable of modulating packing domains, termed Transcriptional Plasticity Regulators (TPRs), could prevent cellular adaptation to chemotherapy. We conducted a proof-of-concept compound screen using live-cell chromatin imaging to identify several TPRs that synergistically enhanced chemotherapy-induced cell death. The most effective TPR significantly improved therapeutic outcomes in a patient-derived xenograft model of ovarian cancer. These findings underscore the central role of chromatin in cellular adaptation to cytotoxic stress and present a framework for enhancing cancer therapies, with broad potential across multiple cancer types.
    Keywords:  Biophysics; cancer; chemotherapy; chromatin; plasticity
    DOI:  https://doi.org/10.1073/pnas.2425319122
  35. ACS Appl Mater Interfaces. 2025 Jul 21.
    Panorama of Conductive Freestanding Biopolymers for Long-Range Charge Transfer: Effect of Chemical Modification and Doping.
    Amalendu Neogi, Somen Mondal.
      The intricate interplay of electron transfer (ET) and proton transfer (PT) across biomaterials extends beyond biology, paving the way for advancements in bioelectronics. These biomaterials, characterized by their biocompatibility, biodegradability, and renewability, offer a promising platform for applications in bioelectronics, biomedical devices, and energy technologies. This review explores the fundamental principles governing PT and ET, including the Grotthuss mechanism, Marcus theory, and relevant quantum mechanical effects. We highlight key advancements in freestanding protein-based biopolymers and their modifications to enhance the conductivity. The discussion begins with an overview of PT and ET theories, followed by synthesis methods for freestanding protein-based biopolymers, emphasizing the role of surface functional groups (oxo-acid and amine), water content, and the incorporation of light-active moieties to improve conductivity in bovine serum albumin (BSA)-based biopolymers. Furthermore, we examine the quantum integration of organic and nanoparticle dopants, such as metal-porphyrins, carbon dots (C-Dots), and C-Dots-based heterostructures within biopolymers, demonstrating their ability to enhance conductivity by establishing synergistic pathways for ionic and electronic charge transport. This analysis provides insights into how structural modifications influence dynamic charge transport, facilitating the development of high-performance bioelectronic devices. By integrating theoretical frameworks with experimental findings, this review illustrates how tuning proton and electron conductance mechanisms can unlock the potential for sustainable, scalable, and multifunctional biomaterials. Ultimately, this work serves as a foundation for interdisciplinary research, bridging materials science, biochemistry, and bioelectronics to enable innovative applications, including biosensors, biomedical devices, energy storage systems, and light-driven transistors.
    Keywords:  Freestanding biopolymer; bioelectronics; bovine serum albumin; long-range conduction; proton and electron transfer
    DOI:  https://doi.org/10.1021/acsami.5c07719
  36. Mater Today Bio. 2025 Aug;33 102085
    Engineering principles of zwitterionic hydrogels: Molecular architecture to manufacturing innovations for advanced healthcare materials.
    Hoang Linh Bui, Hoang Nam Nguyen, Jui-Yang Lai, Chun-Jen Huang.
      Zwitterionic hydrogels have garnered significant attention for their exceptional anti-fouling properties and biocompatibility. These materials have been further enhanced through the incorporation of highly crosslinked 3D networks, endowing them with novel physicochemical characteristics such as stimuli-responsive swelling, ion conductivity, and antibacterial capabilities. In certain cases, zwitterionic motifs can impart self-healing properties for hydrogels, potentially paving the way for the development of functional biomaterials that closely mimic biological tissues. In recent years, we have witnessed substantial efforts from the scientific community to harness the potential of zwitterionic hydrogels for various biomedical applications. This review offers a comprehensive examination of the design principles underlying these materials, spanning from molecular engineering aspects to recent advancements in synthesis routes and fabrication methods. The discussion encompasses the advantages and limitations of different preparation processes, as well as prospects for zwitterionic hydrogels. As a result, this review aims to provide valuable insights for researchers and engineers working to optimize zwitterionic hydrogels for specific biomedical applications, including drug delivery, tissue engineering, and biosensors.
    Keywords:  Biomedical applications; Hydrogel; Molecular design; Preparation process; Zwitterionic
    DOI:  https://doi.org/10.1016/j.mtbio.2025.102085
  37. Proc Natl Acad Sci U S A. 2025 Jul 29. 122(30): e2506353122
    ATP synthesis driven by atmospheric hydrogen concentrations.
    Sarah Soom, Stefan Urs Moning, Gregory M Cook, James P Lingford, Ashleigh Kropp, Sieu Tran, Rhys Grinter, Chris Greening, Christoph von Ballmoos.
      All cells require a continuous supply of the universal energy currency, adenosine triphosphate (ATP), to drive countless cellular reactions. The universally conserved F1Fo-ATP synthase regenerates ATP from ADP and Pi by harnessing a transmembrane electrochemical proton gradient (pmf). Bacteria have evolved diverse pmf-forming strategies using light, organic, and inorganic energy sources. Recently, we proposed that many bacteria survive using atmospheric trace gases to produce ATP when limited for other energy sources. However, direct evidence that atmospheric energy sources are sufficient to generate pmf or drive ATP synthesis is still lacking. Here, we show that the membrane-associated hydrogen:quinone oxidoreductase Huc from Mycobacterium smegmatis can enable ATP synthesis from air. Purified Huc couples H2 oxidation to the reduction of various ubiquinone and menaquinone analogues. We designed a minimal respiratory chain in which Huc interacts with liposomes containing the nonpumping, but pmf-generating, bd-I oxidase and F1Fo-ATP synthase from Escherichia coli. Our experiments show that passive hydrogen exchange from air to solution is sufficient for the electron transfer and pmf generation required to accumulate ATP. By combining continuous culture bioenergetics measurements with theoretical calculations, we show this process is sufficient for mycobacteria to sustain pmf and ATP synthesis (two ATP molecules per H2 oxidized) for maintenance energy requirements during nutrient starvation. These findings confirm that atmospheric energy sources can be dependable 'lifeline' substrates that enable continuous energy conservation during nutrient starvation. In addition, this work provides a unique tool for ATP production in synthetic applications, which unlike other approaches is traceless without by-product accumulation.
    Keywords:  ATP synthesis; aerotrophy; bioenergetics; hydrogenase; synthetic biology
    DOI:  https://doi.org/10.1073/pnas.2506353122
  38. Nat Chem. 2025 Jul 22.
    Bottom-up computational design of shape-selective organic macrocycles for humid CO2 capture.
    Tao Liu, Hang Qu, Sam D Harding, Isaiah Borne, Linjiang Chen, John W Ward, Simon C Weston, Andrew I Cooper.
      The capture of CO2 emissions using porous solids is challenging because polar water molecules bind more strongly in most materials than non-polar CO2 molecules. This is a challenge for both flue gas capture and for direct air capture alike. Here we develop a bottom-up computational screening workflow to calculate the binding energy of 27,446 diverse molecular fragments with both CO2 and water. Most molecules favour water binding, but bent, clip-like aromatic molecules exhibit potential for the desired reverse selectivity. This suggests that aromatic macrocycles with specific shapes can promote multiple weak π-π interactions with CO2 that surpass stronger but less numerous dipole-π interactions with water. We synthesize two water- and acid-stable molecular prisms with triangular and square geometries, as suggested by computation. Experiments confirm that the CO2 capture capacity of these prisms is unaffected by high relative humidity, surpassing the performance of benchmark commercial porous materials.
    DOI:  https://doi.org/10.1038/s41557-025-01873-1
  39. Nature. 2025 Jul 23.
    Precisely defining disease variant effects in CRISPR-edited single cells.
    Yuriy Baglaenko, Zepeng Mu, Michelle Curtis, Hafsa M Mire, Vidyashree Jayanthi, Majd Al Suqri, Cassidy Liu, Ryan Agnew, Aparna Nathan, Annelise Yoo Mah-Som, David R Liu, Gregory A Newby, Soumya Raychaudhuri.
      Genetic studies have identified thousands of individual disease-associated non-coding alleles, but the identification of the causal alleles and their functions remains a critical bottleneck1. CRISPR-Cas editing has enabled targeted modification of DNA to introduce and test disease alleles. However, the combination of inefficient editing, heterogeneous editing outcomes in individual cells and nonspecific transcriptional changes caused by editing and culturing conditions limits the ability to detect the functional consequences of disease alleles2,3. To overcome these challenges, we present a multi-omic single-cell sequencing approach that directly identifies genomic DNA edits, assays the transcriptome and measures cell-surface protein expression. We apply this approach to investigate the effects of gene disruption, deletions in regulatory regions, non-coding single-nucleotide polymorphism alleles and multiplexed editing. We identify the effects of individual single-nucleotide polymorphisms, including the state-specific effects of an IL2RA autoimmune variant in primary human T cells. Multimodal functional genomic single-cell assays, including DNA sequencing, enable the identification of causal variation in primary human cells and bridge a crucial gap in our understanding of complex human diseases.
    DOI:  https://doi.org/10.1038/s41586-025-09313-3
  40. Nat Food. 2025 Jul;6(7): 657-663
    Unrefined plant raw materials are key to nutritious food.
    Till Germerdonk, Andrea Bach, Alejandro G Marangoni, Kim Mishra, Patrick A Rühs.
      Food processing often overlooks nature's complexity, favouring purified raw materials. This excessive purification fosters unsustainable practices and diminishes the taste and nutritional quality of food. Given the current global environmental and health crises, we propose three food innovation principles to embrace the complexity of plant raw materials: (1) leveraging the inherent chemical, physical, biological and nutritional potential of raw materials; (2) applying robust food processes that cope with raw material complexity; and (3) designing food products from field to colon. Adhering to these principles will allow the development of technologies that could transform raw materials into healthier, more sustainable food products.
    DOI:  https://doi.org/10.1038/s43016-025-01195-y
  41. Mater Today Bio. 2025 Aug;33 102035
    Stimuli-responsive hybrid materials for 4D in vitro tissue models.
    Uxue Aizarna-Lopetegui, Sophia C Bittinger, Noa Álvarez, Malou Henriksen-Lacey, Dorleta Jimenez de Aberasturi.
      There is an existing need to develop 3D tissue models which correctly recapitulate healthy and diseased states. The most commonly used techniques focus on simplistic 2D cell culture techniques, themselves incapable of transmitting the complexity of multi-tissue arrangements, and archaic and unnecessary animal models which fail to reproduce species-dependent aspects. The advances in materials science and engineering approaches have opened the possibility to realistically design and even print, in 3D, complex tissue arrangements, aiming to reach full-scale organ printing. Significant improvements have been noted on the spatial and temporal scale, with excellent resolution and overall size being achieved, in addition to models with extensive lifespans. The application of 3D printing to achieve such models has been extensively reviewed. However, there remains an important lack of integration of physical and mechanical cues to achieve tissue responsiveness, aimed to mimic physiological conditions that occur frequently. With this in mind, we have conducted an extensive review of the literature related to stimuli-responsive materials compatible with 3D (bio)printing techniques. Such materials, often termed hybrid materials due to the combination of organic matrices with inorganic actuators, provide "life" to materials, thus adding an extra dimension to the printing technique and coining the term 4D (bio)printing. Examples of healthy cardiovascular, musculoskeletal and neural tissue models that specifically require the incorporation of dynamic features and pathological models are included.
    Keywords:  4D printing; Cell models; Hybrid materials; Nanoparticles; Stimuli
    DOI:  https://doi.org/10.1016/j.mtbio.2025.102035
  42. J R Soc Interface. 2025 Jul;22(228): 20250058
    In situ interfacial shear rheology of fungal films.
    Ciatta Wobill, Samuel Steffen, Daniel Macken, Peter Fischer, Patrick Alberto Rühs.
      Understanding the dynamic film formation of fungi is essential for designing and creating engineered living fungal materials. However, conventional growth measurements often neglect the three-dimensionality of fungal growth and thus only provide scarce information about the transient mechanical properties. In this study, we use interfacial shear rheology (ISR) to investigate the dynamic formation of fungal films. By using ISR we can identify the lag, exponential and stationary phases of fungal growth by measuring the film viscoelasticity. We observed an increase in storage modulus after 2 h before spore germination, most likely caused by the absorption of spores and metabolic by-products during swelling and germination. Modifying the sugar concentration in the liquid growth media allowed for delayed germination while enhancing the exponential propagation speed of fungi, as visible through colony diameter measurements, spectrophotometry and ISR. Furthermore, we were able to observe the film formation through an increase in interfacial moduli as a measure of biomass. In combination with spectrophotometry and colony diameter measurements, ISR provides a complete picture of the transient film formation over 3 days, shedding light on the germination, exponential growth and stationary phase by providing non-destructive, qualitative measures for biomass and quantitative measures for film strength.
    Keywords:  engineered living materials; filamentous fungi; growth measurement; microbial growth stages; mycelium; rheology
    DOI:  https://doi.org/10.1098/rsif.2025.0058
  43. STAR Protoc. 2025 Jul 22. pii: S2666-1667(25)00379-X. [Epub ahead of print]6(3): 103973
    Protocol for assessment of CRISPR base editors and their components in Escherichia coli.
    Rahul Mahadev Shelake, Jae-Yean Kim.
      Base editing (BE) is a CRISPR technique that allows precise nucleobase conversions. However, high expression of BE components is often toxic in Escherichia coli. Here, we present a protocol for analyzing BE at single or multiple target sites using promoter-terminators for single guide RNA (sgRNA) and BE component expression. We describe steps for designing and cloning sgRNA, synthetic target, and BE biomodules. We then detail procedures for BE module assemblage, E. coli transformation, and testing base editors and components. For complete details on the use and execution of this protocol, please refer to Shelake and Kim,1 Shelake et al.,2 and Shelake et al.3.
    Keywords:  Biotechnology and bioengineering; CRISPR; Gene Expression; Molecular Biology
    DOI:  https://doi.org/10.1016/j.xpro.2025.103973
  44. Biofabrication. 2025 Jul 21.
    Genetically programmable wearable devices for precision physiological and molecular monitoring.
    Jin He, Mengdie Fu, Wenyue An, Wenyi Xu, Jieruo Zhou, Yan Chen, Zichun Xia, Zhiwei Jiang, Guoli Yang.
      Wearable devices have emerged as powerful tools for continuous, real-time health monitoring, enabling the detection of biochemical markers in sweat, tears, saliva, and interstitial fluid. However, existing wearable materials are hindered by limited chemical functionality, static sensing capabilities, and insufficient adaptability to dynamic physiological conditions, which restrict their current impact in precision medicine. Recent advancements have focused on integrating genetic engineering and synthetic biology into wearable platforms, resulting in genetically programmable biointerfaces that enhance specificity, responsiveness, and functional versatility in clinical and personalized healthcare settings. Current applications of these bioengineered devices include real-time monitoring of pathogens, hormones, therapeutic drug levels, and physiological behaviors, offering superior precision and adaptability compared to traditional wearable technologies. This review highlights two key engineering approaches driving this field: genetically modified living cells and cell-free synthetic biology systems. While promising, several challenges still limit broader clinical adoption, including biosafety concerns, the instability of biological components, and translational hurdles. Addressing these challenges requires progress in biocompatibility, controlled gene expression, and durable wearable materials. Looking ahead, future research should aim to integrate these biointerfaces with implantable and smart therapeutic systems, develop autonomous biosensors with self-regulatory functions, and further expand their use in personalized medicine and real-time disease management. By bridging genetic programming with wearable diagnostics, these innovations are laying the groundwork for next-generation biohybrid systems designed to advance precision healthcare.&#xD.
    Keywords:  cell-free synthetic biology; genetically modified cells; precision monitoring; wearable devices
    DOI:  https://doi.org/10.1088/1758-5090/adf25a
  45. Adv Sci (Weinh). 2025 Jul 21. e08075
    Cellulosic Functional Bioplastic with Tunable Strength and Toughness Through Heat-Treatment of Dynamic Covalent Networks.
    Xiangyu Tang, Linlin Zhao, Yunfeng Guo, Ying Wang, Zhenke Wei, Xinyan Fan, Zefang Xiao, Haigang Wang, Yanjun Xie, Yonggui Wang.
      The growing environmental crisis caused by petroleum-based polymers has intensified the development of sustainable alternatives, with many biomass-derived polymers demonstrating potential for degradability, renewability, and low carbon footprints, though these properties can vary depending on structure and processing. However, traditional bio-based systems often lack tunability in mechanical properties, making it challenging to achieve both high strength and ductility. Herein, we report a high-performance, recyclable bio-based film (CAF-L) constructed via Diels-Alder dynamic covalent chemistry between furfuryl-functionalized cellulose acetate and maleimide-modified lignin. Thermally responsive dynamic Diels-Alder bonds, activated through heat-treatment, enable programmable network crosslinking that allows a smooth transition between strength- and ductility-dominated regimes, while maintaining high mechanical performance (tensile strength up to 52.3 MPa and elongation at break up to 545%). Structural characterization and molecular simulations reveal that Diels-Alder bond dynamics drive thermally induced structural reorganization of the polymer network, imparting rare adaptivity to biomass-based systems. In addition, CAF-L films exhibit outstanding UV shielding, oxygen barrier properties, and dual-mode recyclability through solvent dissolution and hot pressing. This work provides a scalable platform for constructing mechanically tunable, structurally reconfigurable, and environmentally resilient cellulosic bioplastic for sustainable packaging and circular material systems.
    Keywords:  cellulose; diels‐alder reaction; heat‐treatment; lignin; tunable mechanical
    DOI:  https://doi.org/10.1002/advs.202508075
  46. Nucleic Acids Res. 2025 Jul 19. pii: gkaf693. [Epub ahead of print]53(14):
    A quorum sensing-controlled type I CRISPRi toolkit for dynamically regulating metabolic flux.
    Han Zheng, Chengyao Mao, Siyao Chen, Shidi Hou, Dongchang Sun.
      Synthetic biology advances have enabled dynamic metabolic regulation via quorum sensing (QS) and CRISPR systems. However, the integration of QS with CRISPR-based systems for dynamic control remains largely underexplored. Here, we developed a QS-controlled type I CRISPR interference (QICi) toolkit that modulates target gene expression in response to cell density. By streamlining CRISPR RNA (crRNA) vector construction and optimizing key QS components PhrQ and RapQ, we achieved a twofold enhancement in QICi efficacy. We subsequently implemented the optimized QICi to reprogram Bacillus subtilis for d-pantothenic acid (DPA) and riboflavin (RF) biosynthesis. Dynamic regulation of the citrate synthase gene citZ by QICi, coupled with pantoate pathway engineering, cofactor supply enhancement, and suppression of sporulation, elevated DPA titers to 14.97 g/l in 5-l fed-batch fermentations without precursor supplementation. QICi-mediated metabolic rewiring of key nodes boosted RF production by 2.49-fold. Together, our work provides a robust tool for reprogramming microbial metabolism and advancing sustainable biomanufacturing.
    DOI:  https://doi.org/10.1093/nar/gkaf693
  47. Med Eng Phys. 2025 Aug;pii: S1350-4533(25)00103-1. [Epub ahead of print]142 104384
    Medical devices: Materials, mechanics, and manufacturing.
    Sotiris Korossis, Vadim V Silberschmidt.
      
    DOI:  https://doi.org/10.1016/j.medengphy.2025.104384
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