bims-enlima Biomed News
on Engineered living materials
Issue of 2025–06–08
forty papers selected by
Rahul Kumar, Tallinna Tehnikaülikool
  1. An Emergent Biosynthetic Pathway to Essential Amino Acids by Metabolic Metathesis.
  2. Synthetic Phosphorylation Networks with Fluorescence and Luminescence Expansion.
  3. Information propagation through enzyme-free catalytic templating of DNA dimerization with weak product inhibition.
  4. Meta-adaptive biomaterials: multiscale, spatiotemporal organization and actuation in engineered tissues.
  5. Peptide stereocomplex cross-links for polymer hydrogels.
  6. MOSAIC: A Highly Efficient, One-Step Recombineering Approach to Plasmid Editing and Diversification.
  7. Standardized Quorum Sensing Tools for Gram-Negative Bacteria.
  8. High-throughput metabolic engineering of Yarrowia lipolytica through gene expression tuning.
  9. Engineering Liquid Hierarchical Materials with DNA-Programmed Spherical Nucleic Acids.
  10. Spiers Memorial Lecture: Recent advances (and challenges) in supramolecular gels.
  11. Strategic weakening for holistic strengthening: overstrain-driven synchronous strengthening-toughening in sustainable rubber via "weak" non-covalent networks.
  12. Viscoelastic N‑cadherin-like interactions maintain neural progenitor cell stemness within 3D matrices.
  13. Controlling DNA-RNA strand displacement kinetics with base distribution.
  14. One-Step Surface Functionalization of Hydrogel-Based, Stimulus-Responsive 3D Microstructures for Human Stem Cells.
  15. Precision multiplexed base editing in human cells using Cas12a-derived base editors.
  16. Noncovalent Aggregation for Diverse Properties in Hydrogels: A Comprehensive Review.
  17. Programmable seconds-to-days-long delayed snapping in jumping metashells.
  18. Dynamic Covalent Polymer Networks of Silicone Elastomers via Organoborane Lewis-Pairs.
  19. Material properties of biomolecular condensates emerge from nanoscale dynamics.
  20. Split-and-pool synthesis to generate scalable combinatorial oligonucleotide libraries on magnetic nanoparticles.
  21. Photocurable and 3D Printable Functional Polyesters to Engineer Elastomeric Scaffolds for Biomedical Applications.
  22. Overflow metabolism originates from growth optimization and cell heterogeneity.
  23. Sequential structure probing of cotranscriptional RNA folding intermediates.
  24. Machine-guided dual-objective protein engineering for deimmunization and therapeutic functions.
  25. Charting unknown metabolic reactions by mass spectrometry-resolved stable-isotope tracing metabolomics.
  26. Universal Relationship between Linear Viscoelasticity and Nonlinear Yielding in Soft Materials.
  27. "Pupdates" on proteasomal degradation in bacteria.
  28. Multi ligand sensing by a bacterial histidine kinase through inhibition of dimerization.
  29. Template-free 3D programmable magnetization of soft millirobots induced by interlayer stress.
  30. Genetic Impacts on the Structure and Mechanics of Cellulose Made by Bacteria.
  31. Photochemical synthesis of natural lipids in artificial and living cells.
  32. Catalytically Active Light Printed Microstructures.
  33. Topology in Biological Piezoelectric Materials.
  34. Engineering Considerations for Developing Next-Generation Oligonucleotide Therapeutics.
  35. Dissecting Rate-Limiting Processes in Biomolecular Condensate Exchange Dynamics.
  36. An engineered platform to study the influence of extracellular matrix nanotopography on cell ultrastructure.
  37. Moisture-Absorbing and Antimicrobial Semi-Interpenetrating Polymer Network Hydrogels: An Advanced Medical and Healthcare Material.
  38. Cell shapes decode molecular phenotypes in image-based spatial proteomics.
  39. Anisotropic Growth of Filamentous Fungi in Wood Hydrogel Composites Increases Mechanical Properties.
  40. Nanoscale Synergy: Transforming First Formed Film of Bacterial Cellulose into High-Performance Functional Fibers.
  1. ACS Omega. 2025 May 27. 10(20): 20171-20178
    An Emergent Biosynthetic Pathway to Essential Amino Acids by Metabolic Metathesis.
    Julie Rivollier, Sandrine Gosling, Valérie Pezo, Marie-Pierre Heck, Philippe Marliere.
      An experimental approach to implanting foreign chemical reactions into living cells is to select for the catalytic production of a vital building block such as an amino acid. Alkene metathesis is unknown in extant biochemistry, but it is emerging as a new type of reaction to be catalyzed by protein enzymes. Here, we show how the alkenic amino acid vinylglycine can be generated in a biocompatible reaction from 5-allyloxy-2-amino-pent-3-enoate (APE) by ring-closing metathesis catalyzed by a standard Hoveyda-Grubbs catalyst. The vinylglycine produced in situ is then used as a precursor of isoleucine and methionine, thus allowing the growth of strains of Escherichia coli requiring these essential amino acids. The robust nutritional screen we have developed paves the way for the directed evolution of genetically encoded metathesis enzymes and the chemical elaboration of metathesis coenzymes.
    DOI:  https://doi.org/10.1021/acsomega.4c10463
  2. ACS Synth Biol. 2025 Jun 06.
    Synthetic Phosphorylation Networks with Fluorescence and Luminescence Expansion.
    Leah Davis, Evan J Hutt, Matthias Recktenwald, Samarth Patel, Madison Briggs, Madeline Dunsmore, Sebastián L Vega, Mary M Staehle, Peter A Galie, Nichole M Daringer.
      Synthetic receptors have emerged as powerful tools for precisely modulating cellular function. However, existing synthetic receptor platforms rely mainly on transcription-mediated reporting processes that are incompatible with the rapid and real-time dynamics of cellular signaling events. To address this limitation, we present SPN-FLUX (synthetic phosphorylation networks with fluorescence and luminescence expansion), a fully post-translational platform that integrates synthetic phosphorylation networks with split fluorescent or luminescent proteins, enabling rapid and tunable reporting of cellular processes. SPN-FLUX is responsive to extracellular stimuli within 1 h, providing a robust alternative to transcription-based approaches. Using mammalian cells as a model, we showcase SPN-FLUX's versatility by designing a membrane-bound receptor that activates upon ligand-induced dimerization, as well as a constitutively active intracellular biosensor. We further validate SPN-FLUX's biosensing capabilities by examining its responsiveness to hypoxic conditions, showcasing the ability to detect environmental changes dynamically. The modularity and programmability of SPN-FLUX establish it as a powerful platform for advancing synthetic biology and biosensing, with broad applications in both biomedical research and environmental monitoring.
    Keywords:  biosensing; cell-based devices; programmable synthetic receptors; split fluorescent proteins; split luciferase proteins; synthetic biology
    DOI:  https://doi.org/10.1021/acssynbio.4c00814
  3. Nat Chem. 2025 Jun 05.
    Information propagation through enzyme-free catalytic templating of DNA dimerization with weak product inhibition.
    Javier Cabello-Garcia, Rakesh Mukherjee, Wooli Bae, Guy-Bart V Stan, Thomas E Ouldridge.
      Information propagation by sequence-specific, template-catalysed molecular assembly is a key process facilitating life's biochemical complexity, yielding thousands of sequence-defined proteins from only 20 distinct building blocks. However, exploitation of catalytic templating is rare in non-biological contexts, particularly in enzyme-free environments, where even the template-catalysed formation of dimers is challenging. Typically, product inhibition-the tendency of products to bind to templates more strongly than individual monomers-prevents catalytic turnover. Here we present a rationally designed enzyme-free system in which a DNA template catalyses, with weak product inhibition, the production of sequence-specific DNA dimers. We demonstrate selective templating of nine different dimers with high specificity and catalytic turnover, then we show that the products can participate in downstream reactions, and finally that the dimerization can be coupled to covalent bond formation. Most importantly, our mechanism demonstrates a design principle for constructing synthetic molecular templating systems, a first step towards applying this powerful motif in non-biological contexts to construct many complex molecules and materials from a small number of building blocks.
    DOI:  https://doi.org/10.1038/s41557-025-01831-x
  4. Trends Biotechnol. 2025 Jun 04. pii: S0167-7799(25)00170-2. [Epub ahead of print]
    Meta-adaptive biomaterials: multiscale, spatiotemporal organization and actuation in engineered tissues.
    Gerardo Cedillo-Servin, Essa A A Al-Jehani, Tamara Rossy, Simão P B Teixeira, Fanny Sage, Rui M A Domingues, Ritu Raman, Miguel Castilho.
      Organized cell architecture and dynamic forces are key for (re)creating native-like tissue function (e.g., contractile soft tissues). However, few studies have explored the combined effects of material-guided 3D cell organization with mechanical stimulation. Herein we underscore the importance of converging material-driven guidance of cell organization with stimulus-responsive actuation for multiscale biomaterial design, outlining strategies to engineer such biomaterials. Given the state-of-the-art biomaterials for multiscale spatiotemporally controlled organization and actuation, we propose a synergistic approach ('meta-adaptive biomaterials') that unlocks complexity in engineered biomaterials, harnessing adaptive feedback pathways arising from cell-material interactions. These can be designed similarly to cell-extracellular matrix (ECM) interactions to reinforce user-specified behaviors and yield functionalities that resemble or surpass native tissues, expanding possibilities in tissue engineering, in vitro models, and biohybrid robotics.
    Keywords:  cell–material interactions; embodied intelligence; hierarchical design; interactive biomaterials
    DOI:  https://doi.org/10.1016/j.tibtech.2025.05.004
  5. Chem Sci. 2025 Jun 02.
    Peptide stereocomplex cross-links for polymer hydrogels.
    Israt Jahan Duti, Jonathan Paul, Keelin S Reilly, Darren R Miller, Diane A Dickie, Rachel A Letteri.
      Stereocomplexation, or stereochemistry-directed complexation between complementary stereoregular macromolecules such as polymers and peptides, brings about remarkable changes in the thermomechanical properties and stability of materials. Peptide stereocomplexes tie together these merits of stereocomplexation with the vast compositional space and biological function of peptides, and therefore are compelling building blocks of highly tunable, functional materials. In this work, we introduce peptide stereocomplexes as cross-links in polymer hydrogels. Attaching either l- or d-peptides to 4-arm PEG furnishes conjugates that are soluble in aqueous buffer, while their 1 : 1 blends form hydrogels at or above 7.5% (w/v). Increasing conjugate concentration increases both shear storage modulus (G') and the intensity of the characteristic β-sheet infrared absorption at 1630 cm-1, highlighting the importance of peptide secondary structure for gelation. These gels, having peptide stereocomplexes as cross-links, strain stiffen up to nearly 50% strain, then soften at higher strains. Despite the crystalline nature of stereocomplexes, these gels display dynamic behavior: after application and removal of high strain, the gels recover partially, with 10-50% recovery of G' after the first cycle and 50-70% in subsequent cycles. Moreover, the peptide stereocomplex cross-links imbue proteolytic stability, with nearly 80% of conjugates remaining intact after a 1 h incubation with Proteinase K, compared to just ∼40% of the l-conjugates. We anticipate that the material platform and combination of characterization methods presented here will readily extend to studying other peptides sequences, so as to leverage the full range of peptide design space and accelerate the development and implementation of peptide stereocomplexes to control hydrogel properties, function, and lifetime.
    DOI:  https://doi.org/10.1039/d5sc00251f
  6. ACS Synth Biol. 2025 Jun 05.
    MOSAIC: A Highly Efficient, One-Step Recombineering Approach to Plasmid Editing and Diversification.
    Marijn van den Brink, Timotheus Y Althuis, Christophe Danelon, Nico J Claassens.
      The editing of plasmids and construction of plasmid libraries is paramount to the engineering of desired functionalities in synthetic biology. Typically, plasmids with targeted mutations are produced through time- and resource-consuming DNA amplification and/or cloning steps. In this study, we establish MOSAIC, a highly efficient protocol for the editing of plasmids and generation of combinatorial plasmid libraries. This quick protocol employs the efficient single-stranded DNA annealing protein (SSAP) CspRecT to incorporate (libraries of) DNA oligos harboring the desired mutations into a target plasmid in Escherichia coli. In addition to up to 90% single-target plasmid editing efficiency, we demonstrate that MOSAIC enables the generation of a combinatorial plasmid library spanning four different target regions on a plasmid, in a single transformation. Lastly, we integrated a user-friendly validation pipeline using Nanopore sequencing reads, requiring minimal computational experience. We anticipate that MOSAIC will provide researchers with a simple, rapid and resource-effective method to edit plasmids or generate large, diverse plasmid libraries for a wide range of in vivo or in vitro applications in molecular and synthetic biology.
    Keywords:  MAGE; combinatorial libraries; multiplex; nanopore sequencing; plasmid libraries; recombineering
    DOI:  https://doi.org/10.1021/acssynbio.4c00657
  7. ACS Synth Biol. 2025 Jun 06.
    Standardized Quorum Sensing Tools for Gram-Negative Bacteria.
    Paula Múgica-Galán, Jesús Miró-Bueno, Ángeles Hueso-Gil, Pablo Japón, Ángel Goñi-Moreno.
      Engineering synthetic consortia to perform distributed functions requires robust quorum sensing (QS) systems to facilitate communication between cells. However, the current QS toolbox lacks standardized implementations, which are particularly valuable for use in bacteria beyond the model species Escherichia coli. We developed a set of three QS systems encompassing both sender and receiver modules, constructed using backbones from the SEVA (Standard European Vector Architecture) plasmid collection. This increases versatility, allowing plasmid features like the origin of replication or antibiotic marker to be easily swapped. The systems were characterized using the synthetic biology chassis Pseudomonas putida. We first tested individual modules, then combined sender and receiver modules in the same host, and finally assessed the performance across separate cells to evaluate consortia dynamics. Alongside the QS set, we provide mathematical models and rate parameters to support the design efforts. Together, these tools advance the engineering of robust and predictable multicellular functions.
    Keywords:  bacteria; cell−cell communication; distributed computation; genetic tools; quorum sensing; standards
    DOI:  https://doi.org/10.1021/acssynbio.5c00036
  8. Proc Natl Acad Sci U S A. 2025 Jun 10. 122(23): e2426686122
    High-throughput metabolic engineering of Yarrowia lipolytica through gene expression tuning.
    Wei Jiang, Shengbao Wang, Daniel Ahlheit, Tommaso Fumagalli, Zhijie Yang, Shreemaya Ramanathan, Xinglin Jiang, Tilmann Weber, Jonathan Dahlin, Irina Borodina.
      The challenge of accurately predicting which genetic alternations lead to the desired phenotype necessitates high-throughput metabolic engineering approaches where numerous hypotheses can be tested simultaneously. We describe the CRISPR-Cas9-based method TUNEYALI that enables high-throughput tuning of gene expression in the common industrial yeast Yarrowia lipolytica. The method is based on replacing the promoters of the target genes with native Y. lipolytica promoters of varying strengths or removing the promoters entirely. To demonstrate the method's capabilities, we created a plasmid library that targets 56 transcription factors (TFs) and changes the expression of each TF to seven different levels. We transformed this library into reference and betanin-producing strains of Y. lipolytica and screened the resulting clones for changes in morphology, thermotolerance, or improved betanin production. The genetic markup of the yeast clones with the desired phenotypic changes was determined by sequencing the inserted plasmids. We identified multiple TFs whose regulatory changes increased thermotolerance, two TFs that eliminated pseudohyphal growth, and several TFs that increased betanin production. Analogous libraries can be designed to target any chosen group of genes and even all the genes. The libraries can be shared and reused, accelerating applied strain development projects and fundamental functional genomics research (TUNEYALI-TF kit and TUNEYALI-TF library are available via AddGene under catalog numbers #1000000255 and #217744).
    Keywords:  CRISPR-Cas9; functional genomics; high-throughput genome editing; industrial biotechnology; transcription factors
    DOI:  https://doi.org/10.1073/pnas.2426686122
  9. Adv Sci (Weinh). 2025 Jun 05. e04471
    Engineering Liquid Hierarchical Materials with DNA-Programmed Spherical Nucleic Acids.
    Zeyu Chen, Xu Chen, Dan Lu, Huating Kong, Jingyi Ye, Chunhai Fan, Honglu Zhang, Huan Zhang.
      Inspired by nature, the orchestration of self-assembling building blocks into hierarchical superstructures offers a transformative approach to functional materials design. While significant advances have been made in engineering solid-state hierarchical materials such as crystals and superlattices, creating dynamic, liquid-like hierarchical materials remains a profound challenge. Herein, a universal and efficient method is introduced to construct spherical nucleic acids (SNAs) functionalized with diverse nucleic acids (NAs), including random DNA sequences, circular DNA (circ-DNA), single guide RNA (sgRNA), messenger RNA (mRNA), and multi-branched DNA independent of sequence, length, or topology. By examining spatial configuration and mechanical rigidity in DNA-mediated bonding, precise hierarchical assembly of SNAs is enabled. Furthermore, using these multivalent SNAs as programmable molecule equivalents, liquid-phase hierarchical materials via phase separation are successfully created, forming microscale SNA droplets. These metal condensates exhibit dynamic liquid-like properties and stimuli-responsiveness, including enhanced photothermal effects in living cells. Our findings provide fundamental insights into the formation and dynamics of liquid hierarchical materials, offering potentials for designing living-matter-inspired systems and advancing applications in biomedicine and responsive materials.
    Keywords:  condensate droplets; hierarchical materials; phase separation; spherical nucleic acids
    DOI:  https://doi.org/10.1002/advs.202504471
  10. Faraday Discuss. 2025 Jun 03.
    Spiers Memorial Lecture: Recent advances (and challenges) in supramolecular gels.
    Haozhe Zheng, Darrin J Pochan.
      Supramolecular hydrogels are physical hydrogels that are formed by non-covalent interactions such as hydrogen bonding, electrostatic attraction, hydrophobic interactions, and π-π stacking. Compared to typical, chemically cross-linked hydrogels, supramolecular networks commonly have stimuli-responsive behavior including reversibility and injectability, which are being widely studied for uses in drug delivery, tissue engineering, and wound healing. This review highlights recent developments in supramolecular network design and behavior focusing on the different possible molecular building blocks, including peptides, polysaccharides, synthetic polymers, and multicomponent systems. We further discuss self-assembly mechanisms of hydrogel formation, as well as recent advances in stimuli-responsive supramolecular hydrogels triggered by pH, temperature, and light. Advanced characterization techniques such as rheological analysis, spectroscopy, scattering methods, and electron microscopy are summarized to understand hydrogel structure, assembly pathways, and ultimate network properties. This review provides readers with an updated understanding of supramolecular hydrogels and highlights current research presented during the Faraday Discussions meeting on advances in supramolecular gels, promoting the rational design and development of novel materials to address complex biomedical and other technological challenges.
    DOI:  https://doi.org/10.1039/d5fd00044k
  11. Mater Horiz. 2025 Jun 06.
    Strategic weakening for holistic strengthening: overstrain-driven synchronous strengthening-toughening in sustainable rubber via "weak" non-covalent networks.
    Wei-Chen Zhou, Xue-Qin Gao, Jia-Hao Li, Yan Wang, Yu-Zhong Wang, Cong Deng.
      The pursuit of sustainable rubbers with exceptional mechanical robustness is hindered by intrinsic paradoxes: dynamic covalent networks enable recyclability but compromise mechanical performance, and high-cohesive-energy non-covalent networks are constrained by a fundamental trade-off between strength and ductility. Herein, we introduce a strain amplification paradigm dominated by the purposeful design of non-covalent networks-an approach that strategically engineers stress-bearing pathways through the synergy of reduced cohesive energy and hierarchical interactions. By modulating the cohesive energy of hydrogen-bonding networks in epoxidized natural rubber (ENR), we activate an overstrain-driven stress redistribution mechanism, seamlessly coupling with strain-induced crystallization (SIC) to achieve overstrain-driven strengthening and toughening (ODST)-a counterintuitive yet highly effective strategy for achieving macroscopic robustness. Moreover, implementing the ODST principle in a sustainable rubber via a hierarchy of non-covalent interactions (4U1N-2) yields record-breaking mechanical performance, surpassing state-of-the-art reprocessable rubbers, with a tensile strength of 19.36 MPa, an elongation at break of 1529%, and a toughness of 106.67 MJ m-3. Notably, 4U1N-2 retains substantial mechanical properties after reprocessing, exhibiting performance that exceeds the original properties of most reprocessable rubbers. Moreover, it demonstrates outstanding self-healing capabilities, with strength and elongation at break recovering to 88% and 85%, respectively. This work pioneers a "strategic weakening for holistic strengthening" principle, providing a universal framework for designing high-performance, sustainable elastomers.
    DOI:  https://doi.org/10.1039/d5mh00711a
  12. Nat Commun. 2025 Jun 05. 16(1): 5213
    Viscoelastic N‑cadherin-like interactions maintain neural progenitor cell stemness within 3D matrices.
    Michelle S Huang, Bauer L LeSavage, Sadegh Ghorbani, Aidan E Gilchrist, Julien G Roth, Carla Huerta-López, Esther A Mozipo, Renato S Navarro, Sarah C Heilshorn.
      Neural progenitor cells (NPCs) hold immense potential as therapeutic candidates for neural regeneration, and materials-based strategies have emerged as attractive options for NPC expansion. However, maintaining NPC stemness has proven challenging in vitro, due to their propensity to form cell-dense neurospheres. While neurospheres promote cell-cell interactions required for NPC stem maintenance, they also restrict oxygen transport, leading to hypoxia and limited cell expansion. To overcome these limitations, we investigate two materials-based approaches to maintain NPC stemness: 1) physical matrix remodeling within a viscoelastic, stress-relaxing hydrogel and 2) matrix-induced N-cadherin-like signaling through a cell-instructive peptide. While viscoelasticity alone is sufficient to maintain NPC stemness compared to an elastic environment, NPCs still preferentially form neurospheres. The addition of N-cadherin-like peptides promotes a distributed culture of NPCs while maintaining their stemness through cadherin-mediated signaling, ultimately exhibiting improved long-term expansion and neural differentiation. Thus, our findings reveal matrix viscoelasticity and engineered N-cadherin-like interactions as having a synergistic effect on NPC expansion and differentiation within 3D matrices.
    DOI:  https://doi.org/10.1038/s41467-025-60540-8
  13. Proc Natl Acad Sci U S A. 2025 Jun 10. 122(23): e2416988122
    Controlling DNA-RNA strand displacement kinetics with base distribution.
    Eryk J Ratajczyk, Jonathan Bath, Petr Šulc, Jonathan P K Doye, Ard A Louis, Andrew J Turberfield.
      DNA-RNA hybrid strand displacement underpins the function of many natural and engineered systems. Understanding and controlling factors affecting DNA-RNA strand displacement reactions is necessary to enable control of processes such as CRISPR-Cas9 gene editing. By combining multiscale modeling with strand displacement experiments, we show that the distribution of bases within the displacement domain has a very strong effect on reaction kinetics, a feature unique to DNA-RNA hybrid strand displacement. Merely by redistributing bases within a displacement domain of fixed base composition, we are able to design sequences whose reaction rates span more than four orders of magnitude. We extensively characterize this effect in reactions involving the invasion of dsDNA by an RNA strand, as well as the invasion of a hybrid duplex by a DNA strand. In all-DNA strand displacement reactions, we find a predictable but relatively weak sequence dependence, confirming that DNA-RNA strand displacement permits far more thermodynamic and kinetic control than its all-DNA counterpart. We show that oxNA, a recently introduced coarse-grained model of DNA-RNA hybrids, can reproduce trends in experimentally observed reaction rates. We also develop a simple kinetic model for predicting strand displacement rates. On the basis of these results, we argue that base distribution effects may play an important role in natural R-loop formation and in the function of the guide RNAs that direct CRISPR-Cas systems.
    Keywords:  CRISPR; DNA–RNA hybrids; coarse-grained model; nucleic acid; strand displacement
    DOI:  https://doi.org/10.1073/pnas.2416988122
  14. ACS Appl Mater Interfaces. 2025 Jun 05.
    One-Step Surface Functionalization of Hydrogel-Based, Stimulus-Responsive 3D Microstructures for Human Stem Cells.
    Natalie Munding, Christina Schlagheck, Jochen Wittbrodt, Anthony D Ho, Yoshinori Takashima, Motomu Tanaka.
      To regulate the maintenance and differentiation of stem and progenitor cells, a variety of hydrogels have been developed and applied as two-dimensional (2D) cell culture substrates that can provide well-defined mechanical cues by adjusting the stiffness. Recently, cell-laden hydrogels have been drawing attention as the three-dimensional (3D) cellular environments that can be patterned or printed by extrusion of the cell-polymer mixtures. Hydrogels also serve as 3D microstructures that can stimulate cells both mechanically and geometrically. For flexible, modular functionalization, the coupling of different extracellular matrix (ECM) proteins to side walls and curved surfaces is necessary. However, widely used heterobifunctional photo-cross-linkers encounter a problem because the light cannot reach into the scaffolds uniformly. In this study, we overcame this problem by integrating monomers with N-hydroxysuccinimide (NHS) groups into the copolymer hydrogels with tunable stiffness via careful adjustment of solvent miscibility. This enabled one-step surface functionalization with extracellular matrix proteins such as fibronectin, laminin, and gelatin, replacing photoactivation or laborious multistep functionalization. On the 2D hydrogel substrates functionalized with fibronectin, we found that more than 80% of human mesenchymal stem cells (hMSCs) were viable, and about 60% of them maintained proliferation capacity. These data confirmed that the introduction of NHS monomers caused no cytotoxic effect. We further designed and fabricated 3D microstructures containing various wall and bottom architectures using 3D printed stamps. The uniform functionalization of side walls and bottom surfaces with ECM proteins enabled us to accommodate hMSCs inside the 3D scaffolds, which was in stark contrast to commonly used photo-cross-linkers. The 3D scaffolds showed reversible swelling and deswelling by the addition and removal of soluble guest molecules in the presence of hMSCs, suggesting that the one-step functionalization method established in this study can be applied for a variety of hydrogel-based 3D microstructures for various cell types.
    Keywords:  3D cellular scaffold; human mesenchymal stem cell; polyacrylamide; supramolecular hydrogel; surface functionalization
    DOI:  https://doi.org/10.1021/acsami.5c08146
  15. Nat Commun. 2025 May 31. 16(1): 5061
    Precision multiplexed base editing in human cells using Cas12a-derived base editors.
    Anabel Y Schweitzer, Etowah W Adams, Michael T A Nguyen, Monkol Lek, Farren J Isaacs.
      Base editors enable the direct conversion of target nucleotides without introducing DNA double strand breaks, making them a powerful tool for creating point mutations in a human genome. However, current Cas9-derived base editing technologies have limited ability to simultaneously edit multiple loci with base-pair level precision, hindering the generation of polygenic phenotypes. Here, we test the ability of six Cas12a-derived base editing systems to process multiple gRNAs from a single transcript. We identify base editor variants capable of multiplexed base editing and improve the design of the respective gRNA array expression cassette, enabling multiplexed editing of 15 target sites in multiple human cell lines, increasing state-of-the-art in multiplexing by three-fold in the field of mammalian genome engineering. To reduce bystander mutations, we also develop a Cas12a gRNA engineering approach that directs editing outcomes towards a single base-pair conversion. We combine these advances to demonstrate that both strategies can be combined to drive multiplex base editing with greater precision and reduced bystander mutation rates. Overcoming these key obstacles of mammalian genome engineering technologies will be critical for their use in studying single nucleotide variant-associated diseases and engineering synthetic mammalian genomes.
    DOI:  https://doi.org/10.1038/s41467-025-59653-x
  16. Chem Rev. 2025 Jun 05.
    Noncovalent Aggregation for Diverse Properties in Hydrogels: A Comprehensive Review.
    Sidi Duan, Mutian Hua, Chuan Wei Zhang, Wen Hong, Yichen Yan, Abdullatif Jazzar, Chi Chen, Pengju Shi, Muqing Si, Dong Wu, Zishang Lin, Ping He, Yingjie Du, Ximin He.
      The rapid expansion of hydrogel research over recent decades has bridged fundamental chemistry and physics with advanced materials science applications. This field necessitates comprehensive and in-depth review and discussion of the diverse and rapidly expanding body of research, thereby providing a cohesive understanding that can drive future innovations and applications. This review delves into the role of noncovalent interactions in hydrogel aggregation, a critical mechanism for creating desired microstructures that enhance material properties. Inspired by natural molecular architecture, this paper explores how synthetic hydrogels exploit hydrogen bonds, hydrophobic interactions, and other noncovalent forces to create robust, multifunctional, and water-rich networks. We further discuss methods to induce these interactions and the unique properties resulting from the formed structures. With these methods, we provide insights into the art of manipulating aggregated structures within hydrogels to develop adaptable, tunable materials for a broad range of applications, including bioengineering, robotics and soft electronics, highlighting their significant practical value across interdisciplinary fields.
    DOI:  https://doi.org/10.1021/acs.chemrev.5c00069
  17. Proc Natl Acad Sci U S A. 2025 Jun 10. 122(23): e2503313122
    Programmable seconds-to-days-long delayed snapping in jumping metashells.
    Haitao Qing, Caizhi Zhou, Fangjie Qi, Jie Yin.
      Shape-shifting structures can transform and recover their shapes in response to external stimuli, but they often lack programmable, clock-like control over spatiotemporal deformation and motion, especially after stimuli are removed. Achieving autonomous, time-regulated spatiotemporal motion remains a grand challenge. Here, we present an autonomous delayed-jumping metashell that integrates viscoelastic materials with monostable architected structures to address this limitation. The metashell with tunable prestored elastic energy features an internal time clock enabling programmable autonomous delayed snapping and jumping after actuation removal. The delay spans from seconds to 2.4 d, with jumping heights decreasing from over 9 to 0.5 body heights. We demonstrate its utility in autonomous explosive seed dispersal devices, achieving wide-area omnidirectional distribution with high survival rates. This strategy paves the way for creating autonomous spatiotemporal shape-shifting structures with broad applications in robotics, morphing matter, ecology, and intelligent systems.
    Keywords:  autonomous jumping; delayed snapping; monostability; sustainable seeding devices; viscoelastic shell structure
    DOI:  https://doi.org/10.1073/pnas.2503313122
  18. Chemistry. 2025 Jun 02. e202501595
    Dynamic Covalent Polymer Networks of Silicone Elastomers via Organoborane Lewis-Pairs.
    Edip Ajvazi, Verena Schinegger, Felix Bauer, Diana Drechsler, Patrick Rettenwander, Dominik Kaineder, Milan Kracalik, Oliver Brüggemann, Sabine Hild, Ingrid Graz, Uwe Monkowius, Ian Teasdale.
      Dynamic covalent polymer networks (DCPNs) have been developed in recent years to offer distinctive mechanical properties and shape responsiveness in thermoset materials, thereby bestowing them with desirable characteristics such as self-healing and recyclability. To achieve these desirable properties, dynamic polymers incorporate reversible covalent bonds that enable shape morphing without causing irreversible chemical degradation of the network structure. Lewis pairs (LP), forming coordinate/dative covalent bonds, exhibit a broad range of bond dissociation rates and energies, making them inherently interesting for designing DCPNs. However, LPs have been relatively unexplored as polymer building blocks. Here, we present a straightforward approach to prepare LP-based polymers based on archetypical LPs, and amine-borane adducts with an organoborane functionalised polydimethylsiloxane combined with commercially available Lewis base (LB) polymers. The dynamic behavior of the organoborane-functionalised system and LB polymers is investigated, demonstrating tunable reversibility in cured elastomers. The excess of LB facilitates rapid recapture and reformation of the covalent network, contributing to the system's reversible and self-healing nature. Notably, the system allows easy mixing of different LB polymers, enabling the creation of tuning the system and hence organoborane-based Lewis pairs are demonstrated to be a promising building block for tunable dynamic covalent polymer networks.
    Keywords:  Covalent adaptive networks; Dynamic covalent polymer networks; Lewis pairs; Polydimethylsiloxane: Inorganic polymers
    DOI:  https://doi.org/10.1002/chem.202501595
  19. Proc Natl Acad Sci U S A. 2025 Jun 10. 122(23): e2424135122
    Material properties of biomolecular condensates emerge from nanoscale dynamics.
    Nicola Galvanetto, Miloš T Ivanović, Simone A Del Grosso, Aritra Chowdhury, Andrea Sottini, Daniel Nettels, Robert B Best, Benjamin Schuler.
      Biomolecular condensates form by phase separation of biological polymers and have important functions in the cell-functions that are inherently linked to their physical properties at different scales. A notable aspect of such membraneless organelles is that their viscoelastic properties can vary by orders of magnitude, but it has remained unclear how these pronounced differences are rooted in the nanoscale dynamics at the molecular level. Here, we investigate a series of condensates formed by complex coacervation of highly charged disordered proteins and polypeptides that span about two orders of magnitude in bulk viscosity. We find that their viscosity is highly correlated with protein translational diffusion and nano- to microsecond chain dynamics. Remarkably, analytical relations from polymer physics can predict condensate viscosity from diffusivity and chain dynamics, and vice versa, even for more hydrophobic disordered proteins and for synthetic polyelectrolytes, indicating a mechanistic link across several decades of length- and timescales. Atomistic simulations reveal that the observed differences in friction-a key quantity underlying these relations-reflect differences in interresidue contact lifetimes as a function of arginine content and salt concentration, leading to the vastly different dynamics among condensates. The rapid exchange of interresidue contacts we observe may be a general mechanism for preventing dynamic arrest in compartments densely packed with polyelectrolytes, such as the cell nucleus.
    Keywords:  Rouse model; biomolecular condensates; complex coacervates; intrinsically disordered proteins; protein dynamics
    DOI:  https://doi.org/10.1073/pnas.2424135122
  20. STAR Protoc. 2025 May 30. pii: S2666-1667(25)00265-5. [Epub ahead of print]6(2): 103859
    Split-and-pool synthesis to generate scalable combinatorial oligonucleotide libraries on magnetic nanoparticles.
    John V L Nguyen, Lidija Malic, Christina Nassif, Dillon Da Fonte, Maryam Tabrizian.
      The generation of combinatorial oligonucleotide libraries is desirable for applications such as DNA aptamers, data storage, DNA origami, or synthetic genomes, but conventional libraries present challenges in detection and analysis. Synthesis of unique oligonucleotide sequences on magnetic nanoparticles would enhance the ability to manipulate, recover, and detect them. Here, we present a protocol for generating a scalable combinatorial oligonucleotide library on magnetic nanoparticles using split-and-pool synthesis. We then describe the process for preparing the library for conventional and next-generation sequencing (NGS) DNA sequencing. For complete details on the use and execution of this protocol, please refer to Nguyen et al.1.
    Keywords:  Biotechnology and bioengineering; High-Throughput Screening; Molecular Biology; Molecular/Chemical Probes; Sequencing
    DOI:  https://doi.org/10.1016/j.xpro.2025.103859
  21. Macromol Biosci. 2025 May 30. e00189
    Photocurable and 3D Printable Functional Polyesters to Engineer Elastomeric Scaffolds for Biomedical Applications.
    Xiaochu Ding, Narangerel Gantumur, Bruce P Lee, Ying Grace Chen.
      Photocurable functional block copolyesters are reported to engineer elastomeric scaffolds for biomedical applications. The polymer backbone is organized by soft and stiff blocks. The functional prepolymer is readily crosslinked by thiol-yne click chemistry under ulraviolet light in the presence of a photo-initiator to form a robust elastomer. The elastomers bear both chemical crosslinks and crystal-domain crosslinks to simultaneously tune the materials' properties, such as mechanical properties and degradation rates. The dual crosslinks can more efficiently tune the mechanical properties compared to the chemical crosslink alone. More importantly, the functional prepolymer is photo-printable to construct elastomeric scaffolds with precise control of pore sizes using the state-of-the-art digital light processing technique. With hydroxyls pendant on the backbone, human umbilical vein endothelial cells prefer to grow on the elastomer surface compared to that of a poly(caprolactone) film. It is believed that these functional photo-polyesters will be useful to construct medical devices for bioengineering research.
    Keywords:  biocompatible and biodegradable polyesters; elastomers; photo‐printing; thiol‐yne click chemistry; tissue scaffolds
    DOI:  https://doi.org/10.1002/mabi.202500189
  22. Elife. 2025 Jun 05. pii: RP94586. [Epub ahead of print]13
    Overflow metabolism originates from growth optimization and cell heterogeneity.
    Xin Wang.
      A classic problem in metabolism is that fast-proliferating cells use seemingly wasteful fermentation for energy biogenesis in the presence of sufficient oxygen. This counterintuitive phenomenon, known as overflow metabolism or the Warburg effect, is universal across various organisms. Despite extensive research, its origin and function remain unclear. Here, we show that overflow metabolism can be understood through growth optimization combined with cell heterogeneity. A model of optimal protein allocation, coupled with heterogeneity in enzyme catalytic rates among cells, quantitatively explains why and how cells choose between respiration and fermentation under different nutrient conditions. Our model quantitatively illustrates the growth rate dependence of fermentation flux and enzyme allocation under various perturbations and is fully validated by experimental results in Escherichia coli. Our work provides a quantitative explanation for the Crabtree effect in yeast and the Warburg effect in cancer cells and can be broadly used to address heterogeneity-related challenges in metabolism.
    Keywords:  E. coli; I. orientalis; S. cerevisiae; aerobic glycolysis; cell heterogeneity; computational biology; metabolic strategy; mouse; overflow metabolism; physics of living systems; systems biology; warburg effect
    DOI:  https://doi.org/10.7554/eLife.94586
  23. Nat Commun. 2025 Jun 01. 16(1): 5085
    Sequential structure probing of cotranscriptional RNA folding intermediates.
    Courtney E Szyjka, Skyler L Kelly, Eric J Strobel.
      Cotranscriptional RNA folding pathways typically involve the sequential formation of folding intermediates. Existing methods for cotranscriptional RNA structure probing map the structure of nascent RNA in the context of a terminally arrested transcription elongation complex. Consequently, the rearrangement of RNA structures as nucleotides are added to the transcript can be inferred but is not assessed directly. Here, we describe linked-multipoint Transcription Elongation Complex RNA structure probing (TECprobe-LM), which assesses the cotranscriptional rearrangement of RNA structures by sequentially positioning E. coli RNAP at two or more points within a DNA template so that nascent RNA can be chemically probed. We validate TECprobe-LM by measuring known folding events that occur within the E. coli signal recognition particle RNA, Clostridium beijerinckii pfl ZTP riboswitch, and Bacillus cereus crcB fluoride riboswitch folding pathways. Our findings establish TECprobe-LM as a strategy for observing cotranscriptional RNA folding events directly using chemical probing.
    DOI:  https://doi.org/10.1038/s41467-025-60425-w
  24. Cell Syst. 2025 May 23. pii: S2405-4712(25)00132-2. [Epub ahead of print] 101299
    Machine-guided dual-objective protein engineering for deimmunization and therapeutic functions.
    Eric Wolfsberg, Jean-Sebastien Paul, Josh Tycko, Binbin Chen, Michael C Bassik, Lacramioara Bintu, Ash A Alizadeh, Xiaojing J Gao.
      Cell and gene therapies often express nonhuman proteins, which carry a risk of anti-therapy immunogenicity. An emerging consensus is to instead use modified human protein domains, but these domains include nonhuman peptides around mutated residues and at interdomain junctions, which may also be immunogenic. We present a modular workflow to optimize protein function and minimize immunogenicity by using existing machine learning models that predict protein function and peptide-major histocompatibility complex (MHC) presentation. We first applied this workflow to existing transcriptional activation and RNA-binding domains by removing potentially immunogenic MHC II epitopes. We then generated small-molecule-controllable transcription factors with human-derived DNA-binding domains targeting non-genomic DNA sequences. Finally, we established a workflow for creating deimmunized zinc-finger arrays to target arbitrary DNA sequences and upregulated two therapeutically relevant genes, utrophin (UTRN) and sodium voltage-gated channel alpha subunit 1 (SCN1A), using it. Our modular workflow offers a way to potentially make cell and gene therapies safer and more efficacious using state-of-the-art algorithms.
    Keywords:  protein design; synthetic biology
    DOI:  https://doi.org/10.1016/j.cels.2025.101299
  25. Nat Commun. 2025 May 31. 16(1): 5059
    Charting unknown metabolic reactions by mass spectrometry-resolved stable-isotope tracing metabolomics.
    Yang Gao, Mingdu Luo, Hongmiao Wang, Zhiwei Zhou, Yandong Yin, Ruohong Wang, Beizi Xing, Xiaohua Yang, Yuping Cai, Zheng-Jiang Zhu.
      Metabolic reactions play important roles in organisms such as providing energy, transmitting signals, and synthesizing biomacromolecules. Charting unknown metabolic reactions in cells is hindered by limited technologies, restricting the holistic understanding of cellular metabolism. Using mass spectrometry-resolved stable-isotope tracing metabolomics, we develop an isotopologue similarity networking strategy, namely IsoNet, to effectively deduce previously unknown metabolic reactions. The strategy uncovers ~300 previously unknown metabolic reactions in living cells and mice. Specifically, we elaborately chart the metabolic reaction network related to glutathione, unveiling three previously unreported reactions nestled within glutathione metabolism. Among these, a transsulfuration reaction, synthesizing γ-glutamyl-seryl-glycine directly from glutathione, underscores the role of glutathione as a sulfur donor. Functional metabolomics studies systematically characterize biochemical effects of previously unknown reactions in glutathione metabolism, showcasing their diverse functions in regulating cellular metabolism. Overall, these newly uncovered metabolic reactions fill gaps in the metabolic network maps, facilitating exploration of uncharted territories in cellular biochemistry.
    DOI:  https://doi.org/10.1038/s41467-025-60258-7
  26. Phys Rev Lett. 2025 May 23. 134(20): 208202
    Universal Relationship between Linear Viscoelasticity and Nonlinear Yielding in Soft Materials.
    Daniel P Keane, Elnaz Nikoumanesh, Krutarth M Kamani, Simon A Rogers, Ryan Poling-Skutvik.
      The nonlinear response of yield stress fluids remains difficult to predict and control. Here, we show that the height of the overshoot in the loss modulus G^{''}, a key characteristic of yielding, depends only on linear viscoelastic properties. Furthermore, the position of this overshoot depends on linear viscoelastic and flow properties, demonstrating the important and enduring role of elasticity in yielding. The physics governing linear viscoelasticity is therefore not only preserved during yielding but also controls two commonly reported yielding metrics.
    DOI:  https://doi.org/10.1103/PhysRevLett.134.208202
  27. J Bacteriol. 2025 Jun 05. e0011125
    "Pupdates" on proteasomal degradation in bacteria.
    Shoshanna C Kahne, K Heran Darwin.
      Proteasomes are multi-subunit proteases found in all domains of life. The central components of proteasomal degradation are conserved, but how proteins are targeted to proteasomes diverges significantly. Despite the vast amount of information learned about how proteasomal degradation is regulated in eukaryotes, much less is known about the regulation of proteasome activity in bacteria. In this minireview, we highlight recent findings revealing how and when specific proteins are targeted to bacterial proteasomes, with a focus on ATP-dependent proteolysis.
    Keywords:  Mycobacterium; proteasome; pupylation
    DOI:  https://doi.org/10.1128/jb.00111-25
  28. bioRxiv. 2025 May 18. pii: 2025.05.18.654591. [Epub ahead of print]
    Multi ligand sensing by a bacterial histidine kinase through inhibition of dimerization.
    Gaurav D Sankhe, Jiawei Xing, Merissa Xiao, John Buglino, Huilin Li, Igor B Zhulin, Michael S Glickman.
      Two component systems (TCS) mediate bacterial signal transduction in response to specific environmental conditions. The two components are the sensor kinase (SK), which senses the signal and autophosphorylates on a histidine residue, and a response regulator (RR), which is phosphorylated by the kinase and modifies gene expression. Despite intensive study, the mechanisms of signal sensing by sensor kinases are incompletely defined and the mechanisms by which SKs can sense multiple ligands are unclear. Mycobacterium tuberculosis PdtaS/PdtaR is a soluble TCS pair that participates in the Rip1 signal transduction cascade to control virulence by responding to copper and nitric oxide (NO). In contrast to paradigmatic ligand activated SKs, PdtaS is constitutively active without ligand and directly inhibited by Cu or NO, but it is unclear how such chemically diverse ligands are sensed. Here we show that PdtaS is a dimeric kinase that constitutively autophosphorylates in trans. Cu and NO both inhibit PdtaS phosphorylation by inhibiting dimerization. Phylogenetic analysis of the PdtaS family reveals conservation of the PAS/GAF dimer interface rather than the ligand binding pockets and mutations in the GAF dimer interface that alter dimerization impair multi-ligand sensing both in vitro and in M. tuberculosis cells. These results indicate that a single bacterial kinase can sense chemically diverse inputs through inhibition of dimerization dependent phosphorylation.
    DOI:  https://doi.org/10.1101/2025.05.18.654591
  29. Proc Natl Acad Sci U S A. 2025 Jun 10. 122(23): e2426846122
    Template-free 3D programmable magnetization of soft millirobots induced by interlayer stress.
    Jie Han, Shuideng Wang, Zhiqiang Zheng, Donglei Chen, Wenqi Zhang, Zhi Qu, Mingxing Cheng, Yiqing Yao, Metin Sitti, Lixin Dong.
      Soft magnetic miniature devices are crucial for applications in minimally invasive medicine, soft electronics, and robotics. While substantial progress has been made, current magnetic programming techniques are inherently tied to template-based and sequential fabrication processes. These processes limit scalability, precision, and programmability. Here, we present a template-free, integrative strategy that leverages interlayer stress-induced 3D shape morphing in xerogel-PDMS bilayer materials triggered by temperature variations. This process induces preprogrammed deformation and fixes the 3D structure via interlayer stress and solid-liquid phase transition. It is akin to an insect encased in amber, resulting in a soft machine with precisely tailored magnetic domains upon saturated magnetization. The approach eliminates the need for predesigned molds, which offers scalable, template-free programmable magnetization, reducing time and labor costs. The versatility of this method is demonstrated through reconfigurable mechanical behavior in kirigami metamaterial structures, information encryption, and multilegged millirobots. Moreover, by incorporating a nonmagnetic PDMS layer, laser-based engraving and ablation allow simultaneous control of interlayer stress and material properties. This facilitates precise regulation of stress-induced deformation and magnetically responsive regions with 20 μm resolution and over 1.8 T magnetization strength. This template-free 3D magnetization strategy significantly enhances design flexibility, machining precision, and mass production. It paves the way for advanced multiscale and programmable soft magnetic devices.
    Keywords:  environmental response; magnetic actuation; miniature robot; soft robotics
    DOI:  https://doi.org/10.1073/pnas.2426846122
  30. Adv Sci (Weinh). 2025 Jun 05. e05075
    Genetic Impacts on the Structure and Mechanics of Cellulose Made by Bacteria.
    Julie M Laurent, Mathias Steinacher, Anton Kan, Maximilian Ritter, Mario Leutert, Siiri Bienz, David Häberlin, Naresh Kumar, André R Studart.
      The synthesis of cellulose pellicles by bacteria offers an enticing strategy for the biofabrication of sustainable materials and biomedical devices. To leverage this potential, bacterial strains that overproduce cellulose are identified through directed evolution technology. While cellulose overproduction is linked with a specific genetic mutation, the effect of such mutation on the intracellular protein landscape and on the structure and mechanical properties of the cellulose pellicles is not yet understood. Here, the proteome of bacteria evolved to overproduce cellulose is studied and its effect on the structure and mechanics of the resulting cellulose pellicles is investigated. Proteomic analysis reveals that the protein landscape of the evolved bacteria shows pronounced differences from that of native microorganisms. Thanks to concerted changes in the proteome, the evolved bacteria can generate cellulose pellicles with exquisite structure and improved mechanical properties for applications in textiles, packaging, and medical implants.
    Keywords:  bacterial cellulose; directed evolution; fiber networks; mutations; proteomics
    DOI:  https://doi.org/10.1002/advs.202505075
  31. Nat Commun. 2025 May 31. 16(1): 5068
    Photochemical synthesis of natural lipids in artificial and living cells.
    Peng Ji, Alexander Harjung, Caroline H Knittel, Alessandro Fracassi, Jiyue Chen, Roberto J Brea, Neal K Devaraj.
      Lipid synthesis plays a central role in cell structure, signaling, and metabolism. A general method for the abiogenesis of natural lipids could transform the development of lifelike artificial cells and unlock new ways to explore lipid functions in living cells. Here, we demonstrate the abiotic formation of natural lipids in water using visible-light-driven photoredox chemistry. Radical-mediated coupling of hydrocarbon tails to polar single-chain precursors yields lipids identical to those enzymatically formed. Spatiotemporally controlled lipid generation promotes de novo vesicle formation, growth, and division. Lipid synthesis can be driven by RNA aptamers that specifically bind and activate photocatalysts, establishing a direct link between abiotic lipid metabolism and nucleic acid sequence. Light-mediated assembly of bioactive lipids can take place in living cells, triggering signaling events such as apoptosis and protein kinase C (PKC) activation. Our finding that photochemical lipid synthesis can be driven by simple genetic elements could be the starting point for developing protocells capable of Darwinian evolution. Additionally, the ability to generate specific membrane lipids in living cells with precise spatiotemporal control will advance studies on how lipid structure influences cellular function.
    DOI:  https://doi.org/10.1038/s41467-025-60358-4
  32. Adv Mater. 2025 Jun 06. e2506663
    Catalytically Active Light Printed Microstructures.
    Alicia K Finch, Sebastian Gillhuber, Hendrik Frisch, Peter W Roesky, Christopher Barner-Kowollik.
      Light-induced additive manufacturing (3D printing) has revolutionized manufacturing and its integration into the fabrication of catalysts holds key potential to enable facile access to optimized catalyst geometries and designs. Herein - for the first time - micro- and macro-sized photocatalytically active 3D printed objects are introduced via a dual-function photoresin using a ruthenium(II) complex containing monomer as both a photoinitiator for the 3D printing process and as the active photocatalyst within the printed structure. The approach leverages the spatial and temporal control afforded by light-induced 3D printing techniques during both one- and two-photon printing to precisely position the photocatalyst within intricate geometries using a pentaerythritol triacrylate (PETA) based resin. The successful incorporation of ruthenium(II) complexes is demonstrated via time-of-flight secondary-ion mass spectrometry (ToF-SIMS) into desired sections of 3D-printed objects. The one- and two-photon fabricated architectures show photocatalytic activity in the C─H arylation of activated aryl bromides. The potential of tailored catalytically active 3D objects is exemplified by one of the microscale designs. This design, utilizing only 1% of the volume of a macroscale structure fabricated from the same resin, achieved 75% of the photocatalytic performance.
    Keywords:  3D printing; catalytically active materials; direct laser writing; functional materials; multi‐materials; photocatalysis; stereolithography
    DOI:  https://doi.org/10.1002/adma.202506663
  33. Adv Mater. 2025 Jun 04. e2500466
    Topology in Biological Piezoelectric Materials.
    Chen Chen, Yanhu Zhang, Yi Zheng, Yi Zhang, Hongyi Liu, Jiang Wu, Liang Yang, Zhengbao Yang.
      Topology is fundamental in determining the properties and functions of biological piezoelectric materials by influencing service performances across multiple scales, from nanoscale molecular arrangements to macroscopic assembly structures. At each scale, topology governs electrical, mechanical, and biological behaviors, facilitating multifunctional integration and multi-field coupling advances. Recent progress demonstrates the potential of topological optimization to enhance piezoelectric coefficients and enable complex functionalities. Strategies such as multi-scale design, machine learning-guided optimization, and precision fabrication techniques are being explored to address persistent challenges, including limited energy conversion efficiency, long-term stability, and biocompatibility. Critical applications include health monitoring, biosensing, energy harvesting, and disease treatment, highlighting opportunities and unresolved technical bottlenecks. Future research directions are discussed to present theoretical insights and practical pathways to the development of biological piezoelectric materials.
    Keywords:  biomaterials; energy conversion; energy harvesting; piezoelectric; sensor
    DOI:  https://doi.org/10.1002/adma.202500466
  34. Nat Chem Eng. 2024 Dec;1(12): 741-750
    Engineering Considerations for Developing Next-Generation Oligonucleotide Therapeutics.
    Sasha B Ebrahimi, Himanshu Bhattacharjee, Sujatha Sonti, Doug Fuerst, Patrick S Doyle, Yi Lu, Devleena Samanta.
      Oligonucleotide therapeutics are revolutionizing disease treatment by regulating molecules at the genetic level, offering the possibility of treating conditions that were once considered "undruggable." However, delivering oligonucleotides to tissues beyond the liver remains a key challenge, limiting their clinical applications thus far to niche indications. To achieve broader applicability, extensive biomolecular engineering is necessary to enhance the stability, tissue targetability, pharmacokinetics, and pharmacodynamics of these structures. The intricate design of these molecules also demands sophisticated process engineering techniques. Herein, we provide a collaborative Perspective from academia and industry on the pivotal role of chemical engineering in expanding the use of therapeutic oligonucleotides to treat a wider range of diseases. We discuss how the interplay between biomolecular and process engineering impacts the developability of next-generation oligonucleotide therapeutics as well as their translation from bench to bedside.
    DOI:  https://doi.org/10.1038/s44286-024-00152-z
  35. bioRxiv. 2025 May 22. pii: 2025.05.16.654578. [Epub ahead of print]
    Dissecting Rate-Limiting Processes in Biomolecular Condensate Exchange Dynamics.
    Ross Kliegman, Eli Kengmana, Rebecca Schulman, Yaojun Zhang.
      An increasing number of biomolecules have been shown to phase-separate into biomolecular condensates - membraneless subcellular compartments capable of regulating distinct biochemical processes within living cells. The speed with which they exchange components with the cellular environment can influence how fast biochemical reactions occur inside condensates and how fast condensates respond to environmental changes, thereby directly impacting condensate function. While Fluores-cence Recovery After Photobleaching (FRAP) experiments are routinely performed to measure this exchange timescale, it remains a challenge to distinguish the various physical processes limiting fluorescence recovery and identify each associated timescale. Here, we present a reaction-diffusion model for condensate exchange dynamics and show that such exchange can differ significantly from that of conventional liquid droplets due to the presence of a percolated molecular network, which gives rise to different mobility species in the dense phase. In this model, exchange can be limited by diffusion of either the high- or low-mobility species in the dense phase, diffusion in the dilute phase, or the attachment/detachment of molecules to/from the network at the surface or throughout the bulk of the condensate. Through a combination of analytic derivations and numerical simulations in each of these limits, we quantify the contributions of these distinct physical processes to the overall exchange timescale. Demonstrated on a biosynthetic DNA nanostar system, our model offers insight into the predominant physical mechanisms driving condensate material exchange and provides an experimentally testable scaling relationship between the exchange timescale and condensate size. Interestingly, we observe a newly predicted regime in which the exchange timescale scales nonquadratically with condensate size.
    DOI:  https://doi.org/10.1101/2025.05.16.654578
  36. Nanoscale. 2025 Jun 04.
    An engineered platform to study the influence of extracellular matrix nanotopography on cell ultrastructure.
    Shani Tcherner Elad, Rita Vilensky, Noa Ben Asher, Nataliya Logvina, Ran Zalk, Eyal Zussman, Leeya Engel.
      Nanoscale fabrication techniques have played an essential role in revealing the impact of extracellular matrix (ECM) nanotopography on cellular behavior. However, the mechanisms by which nanotopographical cues from the ECM influence cellular function remain unclear. To approach these questions, we have engineered a novel class of nanopatterned ECM constructs suitable for cryogenic electron tomography (cryo-ET), the highest resolution modality for imaging frozen hydrated cells in 3D. We electrospun aligned and randomly oriented ECM fibers directly onto transmission electron microscopy (TEM) supports to generate fibrous scaffolds that mimic physiological ECM in healthy (organized ECM) and diseased (disorganized ECM) states. We produced fibers from gelatin without toxic additives and cross-linked them to maintain structural stability in aqueous environments. The electrospun fibers had an average fiber diameter of hundreds of nanometers. We confirmed that the nanopatterned TEM supports can serve as viable cell culture substrates that can influence cell organization and demonstrated their compatibility with plunge freezing and cryo-ET. By enabling nanoscale structural analysis inside cells on substrates with programmable topographies, this platform can be used to study the physical cues necessary for healthy endothelial tissue formation and pathologies that are linked to endothelial dysfunction in diseases such as peripheral arterial disease.
    DOI:  https://doi.org/10.1039/d4nr05508j
  37. ACS Appl Bio Mater. 2025 May 31.
    Moisture-Absorbing and Antimicrobial Semi-Interpenetrating Polymer Network Hydrogels: An Advanced Medical and Healthcare Material.
    Ye Xu, Lifang Ma, Yongyu Zha, Jiangzhen Guo, Yubo Fan, Chunjing Tao.
      The moisture absorption and antibacterial properties of medical materials are crucial for their clinical efficacy. However, existing hydrogel materials primarily focus on enhancing single properties, leading to issues, such as poor mechanical strength and limited environmental adaptability. Therefore, the development of medical materials with the dual functions of moisture absorption and antibacterial activity is of significant importance. In this study, inspired by biomimetic multilevel porous design, a semi-interpenetrating hydrogel material (CNSL) was successfully developed by incorporating moisture-absorbing component (LiCl) and antibacterial nanoparticles (SDP-NPs) into carboxymethyl cellulose (CMC) and N-isopropylacrylamide (NIPAm) matrix. The multilevel porous structure mimics the hierarchical pore characteristics of biological systems, optimizing the specific surface area and significantly improving the moisture absorption performance in the humidity range of 15-90% (0.613-5.127 g/g). The temperature-sensitive network enables intelligent water adsorption-desorption cycling. SDP-NPs provide long-lasting antibacterial effects through sustained release within the pores and physical barriers, demonstrating bactericidal rates of 99.77 and 99.83% against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), respectively, in vitro. The CNSL hydrogel effectively achieves humidity regulation and broad-spectrum antibacterial performance, offering a unique design for the development of multifunctional medical dressings and other healthcare products. This research holds significant value in enhancing the infection prevention and control efficacy as well as clinical safety of medical materials and devices.
    Keywords:  antimicrobial; biocompatibility; moisture absorption; multilevel porous structure; semi-interpenetrating polymer network hydrogel
    DOI:  https://doi.org/10.1021/acsabm.5c00586
  38. bioRxiv. 2025 May 16. pii: 2025.05.13.653868. [Epub ahead of print]
    Cell shapes decode molecular phenotypes in image-based spatial proteomics.
    Trang Le, William D Leineweber, Matheus P Viana, Anthony Cesnik, Jan N Hansen, Wei Ouyang, Susanne M Rafelski, Emma Lundberg.
      The diversity of cellular and tissue structures can arise from a few basic cell shapes, which undergo various transformations based on biophysical constraints on cytoskeletal organization. While cellular geometry has been linked with selected biological processes such as polarity, signaling or morphogenesis, the orchestration of the whole proteome in association to cell shape is still poorly understood. In this study, using more than 1 million images of single cells stained for 11,998 proteins across 10 cell lines in the Human Protein Atlas database, we performed an integrated analysis of organelle, pathway and single protein levels in association to a 2D cellular shapespace. We found that cell and nuclear shapes across cell lines exist in a shared continuum. We also found that the subcellular organelle topology varies across cell lines, but remains robust within each cell line's shapespace. At the single protein level, we found that cells of different shapes in the same cell cycle phase might be preparing for different fates, and that many non-cell cycle proteins expressed shape-based abundance variation. Using the same coordinate framework defined by shape, we could analyze the distribution shift of protein spatial localization under drug perturbation.
    DOI:  https://doi.org/10.1101/2025.05.13.653868
  39. ACS Appl Bio Mater. 2025 Jun 06.
    Anisotropic Growth of Filamentous Fungi in Wood Hydrogel Composites Increases Mechanical Properties.
    Ciatta Wobill, Ziyu Zhang, Peter Fischer, Patrick A Rühs.
      There is a rising demand for sustainable, biodegradable, and robust materials in response to growing environmental concerns. Here, we propose using delignified wood as a scaffold for fungal proliferation to obtain wood-fungi composites. The delignification process preserves the fiber directionality inherent to natural wood, enabling fungi to grow along these fibers, enhancing the composites' mechanical properties, and promoting anisotropic fungal growth. The delignified wood was used as a scaffold for the growth of Aspergillus oryzae and Rhizopus oligosporus. Both wood-fungi composites exhibited a higher mechanical strength after fungal proliferation. We used balsa, poplar, and spruce as wood to demonstrate the effects of varying wood architectures. Even though the tensile strengths of all three wood scaffolds were not significantly different, wood scaffolds with lower densities promoted fungal growth. Increasing agar and glucose concentrations were found to significantly enhance tensile strength and Young's modulus. The tensile strength and Young's modulus of wood scaffolds increased from 101 kPa to nearly 103 kPa and 10-3 GPa to nearly 10-1 GPa, respectively. These results highlight the versatile nature of delignified wood as a platform for fungal growth. It offers tunable properties that can be optimized for various applications in composite manufacturing.
    Keywords:  anisotropy; composite material; delignified wood; engineered living materials; mycelium; tensile test
    DOI:  https://doi.org/10.1021/acsabm.5c00374
  40. Small. 2025 Jun 05. e2501880
    Nanoscale Synergy: Transforming First Formed Film of Bacterial Cellulose into High-Performance Functional Fibers.
    Anurag Kumar, Abu Naser Md Ahsanul Haque, Maryam Naebe, Mudrika Khandelwal.
      Bacterial cellulose (BC) biosynthesis is a dynamic process where its 3D nanofibrous network evolves with culture time, offering ample opportunities to tailor the network for specific applications. Herein, BC-derived macrofiber with exceptional mechanical and functional properties is reported. The biosynthesis parameters are set to get the First Formed Film (FFF) at the liquid-air interface on the second day of culture, which has a homogeneous network structure, unlike the layered structures observed in subsequent films. The FFF ultralong nanofibers are converted into macrofiber through controlled plastic deformation and twisting along the fiber length. The resulting fibers exhibit exceptional mechanical properties, including a tensile strength of (2.5 GPa) and a specific strength of (856.16 MPa g⁻¹cm- 3), the highest reported for cellulose-based fibers. The fibers retain approximately 95% of the stiffness of BC nanofibers, demonstrating excellent nanoscale-to-macroscale property transfer. Notably, this high strength is achieved without any chemical modification or cross-linking. Also, FFF hydrogels are functionalized in situ to fabricate magnetic, antibacterial, and conductive fibers. They demonstrate excellent functionality transfer from hydrogel to fiber- positioning them as ideal candidates for surgical sutures and soft robotics applications. This study successfully highlights the synergy between BC biosynthesis and its morphology in designing high-performance materials.
    Keywords:  bacterial cellulose; functional fibers; high‐performance fibers; nanoscale to macroscale; structure‐property correlation
    DOI:  https://doi.org/10.1002/smll.202501880
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