bims-enlima 2025-03-02 papers

bims-enlima

Biomed News

on Engineered living materials

Issue of 2025–03–02
37 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool

Living Fiber Dispersions from Mycelium as a New Sustainable Platform for Advanced Materials.
Hyper-porous encapsulation of microbes for whole cell biocatalysis and biomanufacturing.
Programming Aliphatic Polyester Degradation by Engineered Bacterial Spores.
Size control and oscillations of active droplets in synthetic cells.
Computational biology predicts metabolic engineering targets for increased production of 103 valuable chemicals in yeast.
Multi-material 3D printed composites inspired by nacre: a hard/soft mechanical interplay.
Publisher Correction: Design and regulation of engineered bacteria for environmental release.
Multi-material Volumetric Bioprinting and Plug-and-play Suspension Bath Biofabrication via Bioresin Molecular Weight Tuning and via Multiwavelength Alignment Optics.
Reprogrammable 4D Tissue Engineering Hydrogel Scaffold via Reversible Ion Printing.
Synthetic photoresponsive hydrogels enable in situ control over murine intestinal monolayer differentiation and crypt formation.
Functional gel materials for next-generation electrochromic devices and applications.
ATP-Regulated Formation of Transient Peptide Amphiphiles Superstructures.
A Genetically Encoded Fluorescent Biosensor for Intracellular Measurement of Malonyl-CoA.
Temporal dose inversion properties of adaptive biomolecular circuits.
Design and Synthesis of Hydrolytically Degradable PEG Carbamate, Carbonate, and Ester Derivatives to Induce Reversible Biostasis.
Hierarchical Engineering for Biopolymer-based Hydrogels with Tailored Property and Functionality.
We use 30 billion tonnes of concrete each year - here's how to make it sustainable.
Combining Two Mechanistically Distinct Reactions from a Single Iron Complex: a Tandem Approach to Thermally Stable and Recyclable Polymers.
Nanoscale Biodegradable Printing for Designed Tuneability of Vaccine Delivery Kinetics.
Rapid self-strengthening in double-network hydrogels triggered by bond scission.
All-cellulose resin for 3D printing hydrogels via digital light processing (DLP).
Anti-resonance in developmental signaling regulates cell fate decisions.
Schiff Base-Crosslinked Tetra-PEG-BSA Hydrogel: Design, Properties, and Multifunctional Functions.
Photo-regulated disulfide crosslinking: a versatile approach to construct mucus-inspired hydrogels.
A Novel Gene Synthesis Platform for Designing Functional Protein Polymers.
Injectable pulsatile drug delivery hydrogels: how do we get to the clinic?
TIGR-Tas: A family of modular RNA-guided DNA-targeting systems in prokaryotes and their viruses.
A glycan foldamer that uses carbohydrate-aromatic interactions to perform catalysis.
Droplet-templating soft materials into structured bead-based aerogels with compartmentalized or welded configurations.
Dual-Functional Antimicrobial and Low-Fouling Cellulose Coatings.
Multiscale toughening mechanisms in biomimetic tendon-like hydrogels.
Development of Bioorthogonally Degradable Tough Hydrogels Using Enamine N-Oxide Based Crosslinkers.
DNA Origami Barcodes for Immunostaining.
Directed evolution of a sequence-specific covalent protein tag for RNA labeling.
A Self-Driving Lab for Nano- and Advanced Materials Synthesis.
Nanoparticle transport in biomimetic polymer-linked emulsions.
Functional Design of Peptide Materials Based on Supramolecular Cohesion.

Adv Mater. 2025 Feb 25. e2418464

Living Fiber Dispersions from Mycelium as a New Sustainable Platform for Advanced Materials.

Ashutosh Sinha, Luiz G Greca, Nico Kummer, Ciatta Wobill, Carolina Reyes, Peter Fischer, Silvia Campioni, Gustav Nyström.

  Functional biopolymeric fibers are key building blocks for developing sustainable materials within the growing bioeconomy. However, their flexible use in emerging advanced materials with smart properties typically requires processing methods that may compromise sustainability. Here, a sustainable route to generate living fiber dispersions (LFD) from mycelium that combines the excellent material-forming properties of biopolymeric fibers, and the highly dynamic properties of living materials is proposed. This is showcased by using industrially available liquid culture and mechanical defibrillation methods to generate well-dispersed living mycelium fibers. These fibers can form materials where precursors with good dispersibility and network formation properties are paramount and can harness dynamic properties through growth even in the absence of added nutrients. This is demonstrated in unique living emulsions with 3.6x slower phase separation and in living films with 2.5x higher tensile strength upon growth, the latter vastly outperforming the strongest pure mycelium materials to date. Further, humidity can be used to modulate mechanical properties and to trigger the superhydrophobic patterning of substrates, mechanical actuation, and degradation of lignocellulosic consumer goods at their end of life. In the future, combining synthetic biology with this promising platform for smart materials can expand the horizons for sustainable material manufacturing.

Keywords:  biopolymer fibers; living fibers; living materials; smart materials; sustainability

DOI:  https://doi.org/10.1002/adma.202418464
Microb Cell Fact. 2025 Feb 24. 24(1): 48

Hyper-porous encapsulation of microbes for whole cell biocatalysis and biomanufacturing.

Jingyi Zhang, Keziah Chang, Joyce Tay, Elaine Tiong, Elena Heng, Theresa Seah, Yi Wee Lim, Guangrong Peh, Yee Hwee Lim, Fong Tian Wong, Cyrus W Beh.

  Biocatalysis using whole cell biotransformation presents an alternative approach to producing complex molecules when compared to traditional synthetic chemical processes. This method offers several advantages, including scalability, self-contained co-factor recycling systems, the use of cost-effective raw materials, and reduced purification costs. Notably, biotransformation using microbial consortia provides benefits over monocultures by enhancing biosynthesis efficiency and productivity through division of labor and a reduction in metabolic burden. However, reliably controlling microbial cell populations within a consortium remains a significant challenge. In this work, we address this challenge through mechanical constraints. We describe the encapsulation and immobilization of cells in a hyper-porous hydrogel block, using methods and materials that are designed to be amenable to industrial scale-up. The porosity of the block provides ample nutrient access to ensure good cell viability, while the mechanical properties of the hydrogel matrix were optimized for Escherichia coli encapsulation, effectively limiting their proliferation while sustaining recombinant protein production. We also demonstrated the potential of this method for achieving stable co-cultivation of microbes by maintaining two different microbial strains spatially in a single porous hydrogel block. Finally, we successfully applied encapsulation to enable biotransformation in a mixed culture. Unlike its non-encapsulated counterpart, encapsulated E. coli expressing RadH halogenase achieved halogenation of the genistein substrate in a co-culture with genistein-producing Streptomyces. Overall, our strategy of controlling microbial cell populations through physical constraints offers a promising approach for engineering synthetic microbial consortia for biotransformation at an industrial scale.

Keywords:  Biocatalysis; Cell immobilization; Co-culture; Microencapsulation

DOI:  https://doi.org/10.1186/s12934-025-02675-3
Biomacromolecules. 2025 Feb 24.

Programming Aliphatic Polyester Degradation by Engineered Bacterial Spores.

Ziyu Cui, Masamu Kawada, Yue Hui, Seunghyun Sim.

Enzymatic degradation of plastics is a sustainable approach to address the growing issue of plastic accumulation. Here, we demonstrate the degradation of aliphatic polyesters using enzyme-displaying bacterial spores and the fabrication of self-degradable spore-containing plastics. The degradation proceeds without nutrient-dependent spore germination into living cells. Engineered spores completely degrade aliphatic polyesters into small molecules, retain activity through multiple cycles, and regain full activity through germination and sporulation. We also found that the interplay between the glass transition temperature and melting temperature of polyester substrates affects heterogeneous biocatalytic degradation by engineered spores. Directly incorporating spores into polyesters results in robust materials that are completely degradable. Our study offers a straightforward and sustainable biocatalytic approach to plastic degradation.

DOI: https://doi.org/10.1021/acs.biomac.4c01652
Nat Commun. 2025 Feb 26. 16(1): 2003

Size control and oscillations of active droplets in synthetic cells.

Judit Sastre, Advait Thatte, Alexander M Bergmann, Michele Stasi, Marta Tena-Solsona, Christoph A Weber, Job Boekhoven.

Oscillations in the formation and dissolution of molecular assemblies inside living cells are pivotal in orchestrating various cellular functions and processes. However, designing such rhythmic patterns in synthetic cells remains a challenge. Here, we demonstrate the spontaneous emergence of spatio-temporal oscillations in the number of droplets, size, and their spatial distribution within a synthetic cell. The coacervate-based droplets in these synthetic cells sediment and fuse at the cell's bottom. Through a size control mechanism, the sedimented, large droplets shrink by expelling droplet material. The expelled molecules nucleate new droplets at the top of the synthetic cell, which grow and sediment again. These oscillations are sustained by converting chemical fuel into waste and can continue for hundreds of periods without evidence of fatigue. Strikingly, the period of the oscillation is in the minute's regime and tunable. The design of oscillating artificial organelles in synthetic cells brings us closer to creating more life-like materials and de novo life.

DOI: https://doi.org/10.1038/s41467-025-57240-8
Proc Natl Acad Sci U S A. 2025 Mar 04. 122(9): e2417322122

Computational biology predicts metabolic engineering targets for increased production of 103 valuable chemicals in yeast.

Iván Domenzain, Yao Lu, Haoyu Wang, Junling Shi, Hongzhong Lu, Jens Nielsen.

  Development of efficient cell factories that can compete with traditional chemical production processes is complex and generally driven by case-specific strategies, based on the product and microbial host of interest. Despite major advancements in the field of metabolic modeling in recent years, prediction of genetic modifications for increased production remains challenging. Here, we present a computational pipeline that leverages the concept of protein limitations in metabolism for prediction of optimal combinations of gene engineering targets for enhanced chemical bioproduction. We used our pipeline for prediction of engineering targets for 103 different chemicals using Saccharomyces cerevisiae as a host. Furthermore, we identified sets of gene targets predicted for groups of multiple chemicals, suggesting the possibility of rational model-driven design of platform strains for diversified chemical production.

Keywords:  genome scale modeling; metabolic engineering; synthetic biology; yeast

DOI:  https://doi.org/10.1073/pnas.2417322122
Sci Rep. 2025 Feb 25. 15(1): 6728

Multi-material 3D printed composites inspired by nacre: a hard/soft mechanical interplay.

Marco Curto, Jack Dowsett, Alexander P Kao, Gianluca Tozzi, Asa H Barber.

  Structural materials are used extensively in nature where mechanical function is required. These structures are composites consisting of soft and, in some cases, hard phases precisely distributed over different length scales. Bio-inspiration aims at producing materials with structure, design and/or mechanical properties adopted from biological tissues. To reproduce complex structures found in nature, additive manufacturing (AM) using three-dimensional printing (3DP) is an attractive method to assemble complex topologies with resolutions approaching the micro and nano-composition. Specifically, high-resolution MultiJetPrinting (MJP) 3D printing allows the simultaneous deposition of soft and hard photo curable plastic resins. Nacre is a prevalent example of a complex biological composite material organization that can test the ability of MJP to manufacture a bio-inspired engineering structure, where the organization of materials in nacre is optimized to avoid catastrophic failure. The ability to generate complex 3D organizations required to mimic the structure of nacre by controlled organization of soft and hard materials is achieved here using a generative design approach. Such a generative design is further enhanced by incorporating two differing MJP directions that provide relatively strong and weak interfaces between the soft and hard material phases. Consideration of classical stress transfer theory between at a hard material reinforcement interface was shown to correlate with experimental observations of mechanical performance and failure in 3D printed nacre inspired composites. Thus, the ability to distribute materials with a range of mechanical properties and incorporate further interfacial design is demonstrated. The approach presented is flexible and allows complex bio-inspired composites to be 3D printed that incorporate different interfacial quality through changing printing direction.

Keywords:  3D printing; Additive manufacturing; Bioinspired; Composites; Multi-material; X-ray tomography

DOI:  https://doi.org/10.1038/s41598-025-91080-2
Nat Microbiol. 2025 Feb 24.

Publisher Correction: Design and regulation of engineered bacteria for environmental release.

Yonatan Chemla, Connor J Sweeney, Christopher A Wozniak, Christopher A Voigt.

DOI: https://doi.org/10.1038/s41564-025-01956-2
Adv Mater. 2025 Feb 26. e2409355

Multi-material Volumetric Bioprinting and Plug-and-play Suspension Bath Biofabrication via Bioresin Molecular Weight Tuning and via Multiwavelength Alignment Optics.

Davide Ribezzi, Jan-Philip Zegwaart, Thomas Van Gansbeke, Aitor Tejo-Otero, Sammy Florczak, Joska Aerts, Paul Delrot, Andreas Hierholzer, Martin Fussenegger, Jos Malda, Jos Olijve, Riccardo Levato.

  Volumetric Bioprinting (VBP), enables to rapidly build complex, cell-laden hydrogel constructs for tissue engineering and regenerative medicine. Light-based tomographic manufacturing enables spatial-selective polymerization of a bioresin, resulting in higher throughput and resolution than what is achieved using traditional techniques. However, methods for multi-material printing are needed for broad VBP adoption and applicability. Although converging VBP with extrusion bioprinting in support baths offers a novel, promising solution, further knowledge on the engineering of hydrogels as light-responsive, volumetrically printable baths is needed. Therefore, this study investigates the tuning of gelatin macromers, in particular leveraging the effect of molecular weight and degree of modification, to overcome these challenges, creating a library of materials for VBP and Embedded extrusion Volumetric Printing (EmVP). Bioresins with tunable printability and mechanical properties are produced, and a novel subset of gelatins and GelMA exhibiting stable shear-yielding behavior offers a new, single-component, ready-to-use suspension medium for in-bath printing, which is stable over multiple hours without needing temperature control. As a proof-of-concept biological application, bioprinted gels are tested with insulin-producing pancreatic cell lines for 21 days of culture. Leveraging a multi-color printer, complex multi-material and multi-cellular geometries are produced, enhancing the accessibility of volumetric printing for advanced tissue models.

Keywords:  biofabrication; embedded printing; hydrogels; pancreas tissue engineering; volumetric additive manufacturing

DOI:  https://doi.org/10.1002/adma.202409355
bioRxiv. 2025 Feb 15. pii: 2025.02.11.637741. [Epub ahead of print]

Reprogrammable 4D Tissue Engineering Hydrogel Scaffold via Reversible Ion Printing.

Aixiang Ding, Fang Tang, Eben Alsberg.

Shape changeable hydrogel scaffolds recapitulating morphological dynamism of native tissues have emerged as an elegant tool for future tissue engineering (TE) applications, due to their capability to create morphodynamical tissues with complex architectures. Hydrogel scaffolds capable of preprogrammable, reprogrammable and/or reversible shape transformations would widely expand the scope of possible temporal shape changes. Current morphable hydrogels are mostly based on multimaterial, multilayered structures, which involve complicated and time-consuming fabrication protocols, and are often limited to single unidirectional deformation. This work reports on the development of a transformable hydrogel system using a fast, simple, and robust fabrication approach for manipulating the shapes of soft tissues at defined maturation states. Simply by using an ion-transfer printing (ITP) technology (i.e., transferring Ca 2+ from an ion reservoir with filter paper and subsequent covering on a preformed alginate-derived hydrogel), a tunable Ca 2+ crosslinking density gradient across the hydrogel thickness has been incorporated, which enables preprogrammable deformations upon further swelling in cell culture media. Combining with a surface patterning technology, cell-laden constructs (bioconstructs) capable of morphing in multiple directions are deformed into sophisticated configurations. Not only can the deformed bioconstructs recover their original shapes by chemical treatment, but at user-defined times they can also be incorporated with new, different spatially controlled gradient crosslinking via the ITP process, conferring 3D bioconstruct shape reprogrammability. In this manner, unique "3D-to-3D" shape conversions have been realized. Finally, we demonstrated effective shape manipulation in engineered cartilage-like tissue constructs using this strategy. These morphable scaffolds may advance 4D TE by enabling more sophisticated spatiotemporal control over construct shape evolution.

DOI: https://doi.org/10.1101/2025.02.11.637741
Adv Funct Mater. 2025 Jan 15. pii: 2413778. [Epub ahead of print]35(3):

Synthetic photoresponsive hydrogels enable in situ control over murine intestinal monolayer differentiation and crypt formation.

Mark W Young, Colter E Oroke, Bruce E Kirkpatrick, Michael R Blatchley, Peter J Dempsey, Kristi S Anseth.

  As a model of the intestinal epithelium, intestinal stem cells (ISCs) have been grown and differentiated as monolayers on materials where stochastic organization of the crypt and villi cells occurs. We developed an allyl sulfide crosslinked photoresponsive hydrogel with a shear modulus of 1.6 kPa and functionalized with GFOGER, Bm-binder peptide ligands for monolayer growth of ISCs. The allyl sulfide chemistry allowed in situ control of mechanics in the presence of growing ISC monolayers, and structured irradiation afforded spatial regulation of the hydrogel properties. Specifically, ISC monolayers grown on 1.6 kPa substrates were in situ softened to 0.29 kPa, using circular patterns 50, 75, and 100 μm in diameter, during differentiation, resulting in control over the size and arrangement of de novo crypts and monolayer cellularity. These photoresponsive materials should prove useful in applications ranging from studying crypt evolution to drug screening and transport across tissues of changing cellular composition.

Keywords:  Allyl Sulfide; Hydrogel; Intestinal stem cell

DOI:  https://doi.org/10.1002/adfm.202413778
Chem Soc Rev. 2025 Feb 28.

Functional gel materials for next-generation electrochromic devices and applications.

Yuyang Wang, Xiaoyan Sun, Quanbing Liu, Guihua Yu.

Flexible, wearable, bistable displays, visualized energy storage devices and large-area smart windows based on electrochromic (EC) technology are regarded as promising next-generation sustainable display technologies, with the potential to improve people's lives by enabling low-energy consumption, vision-friendly, smart display, and energy-efficient building solutions. Recently, gel-based EC devices have gained considerable research interest and have emerged as an effective platform for EC applications due to their unique and enhanced properties. Compared to solid-state and liquid-state EC devices, gel-based EC systems offer superior processability and scalability, improved mechanical properties such as flexibility and stretchability, and high ionic conductivity without leakage or volatility issues. This review summarizes and analyzes the gelation chemistry in EC systems, focusing on their relationship with key EC properties of the device. Ionic conductivity, temperature adaptability, and mechanical characteristics of the gels such as stretchability, self-healing ability, flexibility, and viscosity are foundational for enabling diverse functional EC applications. We introduce the preparation methods of related gels for EC devices and then discuss the factors influencing the properties and the strategies for tuning them, including the control of morphology, network architecture, polymer skeletons, functional groups, and additives within ion gels. Representative and latest applications of gel-based electrolytes in EC devices for various promising displays were then presented. Finally, we critically analyze the remaining challenges that need to be addressed to enable the practical deployment of gel-based EC devices and offer more insights into future directions for advancing EC technologies.

DOI: https://doi.org/10.1039/d4cs01256a
Small. 2025 Feb 25. e2410850

ATP-Regulated Formation of Transient Peptide Amphiphiles Superstructures.

David Cappelletti, Federico Lancia, Andrea Basagni, Luka Đorđević.

  Self-assembly of biotic systems serves as inspiration for the preparation of synthetic supramolecular assemblies to mimic the structural, temporal, and functional aspects of living systems. Despite peptide amphiphiles (PAs) being widely studied in the context of biomimetic and bioactive functional nanomaterials, very little is currently known about the reversible and spatiotemporal control of their hierarchical self-assemblies. Here, it is shown that PA-based supramolecular nanofibers can transiently form superstructures, through binding with oppositely charged adenosine triphosphate (ATP), leading to charge screening and stabilization of bundled nanofibers. Enzymatic hydrolysis of ATP to adenosine monophosphate and phosphates causes the disassembly of the superstructures and recovery of individual nanofibers. The lifetime of superstructures can be controlled by adjusting the concentration of either ATP or enzyme. The role that the formation of bundled PA nanofibers has on chemical reactivity and catalysis is also evaluated. It is observed that superstructuration is responsible for downregulation in the PA activity, which can then be recovered by gradual disassembly of the bundles. These results demonstrate the potential of reversible and controlled hierarchical self-assembly to modulate the reactivity and catalysis of peptide nanostructures.

Keywords:  ATP; nanostructures; peptide amphiphiles; supramolecular chemistry; systems chemistry

DOI:  https://doi.org/10.1002/smll.202410850
ACS Bio Med Chem Au. 2025 Feb 19. 5(1): 184-193

A Genetically Encoded Fluorescent Biosensor for Intracellular Measurement of Malonyl-CoA.

Brodie L Ranzau, Tiffany D Robinson, Jack M Scully, Edmund D Kapelczak, Teagan S Dean, Tara TeSlaa, Danielle L Schmitt.

Malonyl-CoA is the essential building block of fatty acids and regulates cell function through protein malonylation and allosteric regulation of signaling networks. Accordingly, the production and use of malonyl-CoA is finely tuned by the cellular energy status. Most studies of malonyl-CoA dynamics rely on bulk approaches that take only a snapshot of the average metabolic state of a population of cells, missing out on heterogeneous differences in malonyl-CoA and fatty acid biosynthesis that could be occurring among a cell population. To overcome this limitation, we have developed a genetically encoded fluorescent protein-based biosensor for malonyl-CoA that can be used to capture malonyl-CoA dynamics in single cells. This biosensor, termed Malibu (malonyl-CoA intracellular biosensor to understand dynamics), exhibits an excitation-ratiometric change in response to malonyl-CoA binding. We first used Malibu to monitor malonyl-CoA dynamics during inhibition of fatty acid biosynthesis using cerulenin in Escherichia coli, observing an increase in Malibu response in a time- and dose-dependent manner. In HeLa cells, we used Malibu to monitor the impact of fatty acid biosynthesis inhibition on malonyl-CoA dynamics in single cells, finding that two inhibitors of fatty acid biosynthesis, cerulenin and orlistat, which inhibit different steps of fatty acid biosynthesis, increase malonyl-CoA levels. Altogether, we have developed a new genetically encoded biosensor for malonyl-CoA, which can be used to study malonyl-CoA dynamics in single cells, providing an unparalleled view into fatty acid biosynthesis.

DOI: https://doi.org/10.1021/acsbiomedchemau.4c00103
bioRxiv. 2025 Feb 11. pii: 2025.02.10.636967. [Epub ahead of print]

Temporal dose inversion properties of adaptive biomolecular circuits.

Eiji Nakamura, Franco Blanchini, Giulia Giordano, Alexander Hoffmann, Elisa Franco.

Cells have the capacity to encode and decode information in the temporal features of molecular signals. Many pathways, for example, generate either sustained or pulsatile responses depending on the context, and such diverse temporal behaviors have a profound impact on cell fate. Here we focus on how molecular pathways can convert the temporal features of dynamic signals, in particular how they can convert transient signals into persistent downstream events and vice versa. We describe this type of behavior as temporal dose inversion, and we demonstrate that it can be achieved through adaptive molecular circuits. We consider motifs known as incoherent feedforward loop (IFFL) and negative feedback loop (NFL), and identify parametric conditions that enable temporal dose inversion. We next consider more complex versions of these circuits that could be realized using enzymatic signaling and gene regulatory networks, finding that both circuits can exhibit temporal dose inversion. Finally, we consider a generalized IFFL topology, and we find that both the time delay in the inhibition pathway and the relative signal intensities of the activation and inhibition signals are key determinants for temporal dose inversion. Our investigation expands the potential use of adaptive circuits as signal processing units and contributes to our understanding of the role of adaptive circuits in nature.

DOI: https://doi.org/10.1101/2025.02.10.636967
Biomacromolecules. 2025 Feb 25.

Design and Synthesis of Hydrolytically Degradable PEG Carbamate, Carbonate, and Ester Derivatives to Induce Reversible Biostasis.

Gopal Reddy Sama, Meagan N Arguien, Timothy E Hoffman, Benjamin D Fairbanks, Marianela Trujilo-Lemon, Sean Keyser, Kristi S Anseth, Sabrina L Spencer, Christopher N Bowman.

Control over network chemistry and connectivity of hydrogels is critical for the generation of tunable material properties, including material degradation for applications such as tissue scaffolding and drug delivery. Here, the degradation of hydrogels employing different hydrolytically cleavable groups including benzamide and syringic acid-derived carbamates, kojic acid-derived carbonates, and kojic acid-derived esters under physiological conditions was studied. Tunability of the hydrogel network degradation was demonstrated by varying the hydrolytically degradable moiety, macromer functionality, and copolymerization with hydrolytically stable macromers. These hydrolytically labile macromers were introduced and cross-linked intracellularly to induce transient cellular quiescence in MCF10A cells, resulting in a highly tunable degradation mechanism that is shown to be capable of inducing reversible biostasis of cells with 60% of cells treated with the carbonate macromer returning to their proliferative state and rebounding in translational activity after 72 h, while the biological activity of the carbamate macromer-treated cells remained suppressed.

DOI: https://doi.org/10.1021/acs.biomac.4c01607
Adv Mater. 2025 Feb 25. e2414897

Hierarchical Engineering for Biopolymer-based Hydrogels with Tailored Property and Functionality.

Chuan Wei Zhang, Muqing Si, Chi Chen, Ping He, Zhangqing Fei, Nathan Xu, Ximin He.

  Biopolymer-based hydrogels offer versatility in biomedical engineering due to their abundance, biocompatibility, tailorable properties, and environmental responsiveness. Realizing their full potential requires understanding the molecular-level design principles that govern their macroscopic behavior. This review analyzes recent advances in the molecular engineering of biopolymer-based hydrogels, emphasizing innovative network design strategies and processing methods for precise control over material properties and functions. How molecular design influences hydrogel behavior across multiple length scales are explored, focusing on: 1) network design strategies: approaches like double networks, interpenetrating networks, and supramolecular assemblies to tailor mechanical and responsive properties; 2) processing techniques: methods such as Hofmeister effect-induced chain aggregating, cononsolvency-based porous structure controlling, and directional freezing-induced network alignment to achieve hierarchical and anisotropic structures. How these design principles and processing methods influence critical hydrogel properties like mechanical strength, inner mass transportation, and degradation are discussed. The review also covers advanced fabrication techniques that leverage these molecular engineering approaches to create complex, functional hydrogels. By elucidating the relationships between molecular architecture, processing methods, and resulting material properties, this work aims to provide a framework for designing next-generation biopolymer-based hydrogels with enhanced performance and functionality across various applications.

Keywords:  biomedical applications; biopolymer‐based hydrogels; hierarchical structuring; molecular engineering; structure‐property relationships

DOI:  https://doi.org/10.1002/adma.202414897
Nature. 2025 Feb;638(8052): 888-890

We use 30 billion tonnes of concrete each year - here's how to make it sustainable.

Jianzhuang Xiao, Shuai Zou, Chi Sun Poon, Man Lung Sham, Zongjin Li, Surendra P Shah.



Keywords:  Chemistry; Engineering; Policy; Sustainability

DOI:  https://doi.org/10.1038/d41586-025-00568-4
Angew Chem Int Ed Engl. 2025 Feb 28. e202418908

Combining Two Mechanistically Distinct Reactions from a Single Iron Complex: a Tandem Approach to Thermally Stable and Recyclable Polymers.

Kanokon Upitak, Christophe M Thomas.

  A shift from petrochemical feedstocks to renewable resources has the potential to address some of the environmental concerns associated with petrochemical extraction, thereby making the production of plastics a sustainable process. Consequently, there is a growing interest in the development of selective techniques for the conversion of abundant renewable feedstocks into environmentally friendly polymers. We present a one-pot iron-based catalytic system, which is active, efficient, and selective under mild conditions for producing of renewable copolymers. We demonstrate that this system can function as a tandem catalyst for the production of poly(silylether)s, followed by the ring-opening polymerization of lactide. This effective approach provides direct access to novel thermally stable copolymers. Furthermore, we detail the quantitative chemical recycling of such copolymers, underscoring their potential as new environmentally friendly materials.

Keywords:  Poly(silylether)s; Recyclability; Renewable Polymers; catalysis; polylactide

DOI:  https://doi.org/10.1002/anie.202418908
Adv Mater. 2025 Feb 28. e2417290

Nanoscale Biodegradable Printing for Designed Tuneability of Vaccine Delivery Kinetics.

David J Peeler, Rujie Sun, Ceren Kütahya, Patrick Peschke, Kun Zhou, Giulia Brachi, Jonathan Yeow, Omar Rifaie-Graham, Jonathan P Wojciechowski, Thomas F F Fernandez Debets, Vernon LaLone, Xin Song, Krunal Polra, Paul F McKay, John S Tregoning, Robin J Shattock, Molly M Stevens.

  Two-photon polymerization (2PP) 3D printing enables top-down biomaterial synthesis with nanoscale spatial resolution for de novo design of monodisperse injectable drug delivery systems. Spatiotemporal Controlled Release Inks of Biocompatible polyEsters (SCRIBE) is a novel poly(lactic-co-glycolic acid)-triacrylate resin family with sub-micron resolution and tuneable hydrolysis that addresses the limitations of current 2PP resins. SCRIBE enables the direct printing of hollow microparticles with tuneable chemistry and complex geometries inaccessible to molding techniques, which are used to engineer controlled protein release in vitro and in vivo. SCRIBE microparticles are used to modulate antibody titers and class switching as a function of antigen release rate and extend these findings to enable a single-injection vaccine formulation with extended antibody induction kinetics. Demonstrating how the chemistry and computer-aided design of 2PP-printed microparticles can be used to tune responses to biomacromolecule release in vivo opens significant opportunities for a new generation of drug delivery vehicles.

Keywords:  3D printing; immunoengineering; two photon polymerization; vaccine delivery

DOI:  https://doi.org/10.1002/adma.202417290
Nat Mater. 2025 Feb 26.

Rapid self-strengthening in double-network hydrogels triggered by bond scission.

Zhi Jian Wang, Wei Li, Xueyu Li, Tasuku Nakajima, Michael Rubinstein, Jian Ping Gong.

The scission of chemical bonds in materials can lead to catastrophic failure, with weak bonds typically undermining the materials' strength. Here we demonstrate how weak bonds can be leveraged to achieve self-strengthening in polymer network materials. These weak sacrificial bonds trigger mechanochemical reactions, forming new networks rapidly enough to reinforce the material during deformation and significantly improve crack resistance. This rapid strengthening exhibits strong rate dependence, dictated by the interplay between bond breaking and the kinetics of force-induced network formation. As the network formation is generally applicable to diverse monomers and crosslinkers with different kinetics, a wide range of mechanical properties can be obtained. These findings may inspire the design of tough polymer materials with on-demand, rate-dependent mechanical behaviours through mechanochemistry, broadening their applications across various fields.

DOI: https://doi.org/10.1038/s41563-025-02137-6
Int J Biol Macromol. 2025 Feb 21. pii: S0141-8130(25)01940-3. [Epub ahead of print]306(Pt 1): 141389

All-cellulose resin for 3D printing hydrogels via digital light processing (DLP).

Rute Silva, Rafael C Rebelo, Carlos T B Paula, Patrícia Pereira, Ana C Fonseca, Arménio C Serra, Jorge F J Coelho.

  3D printing has emerged as a transformative technology in sustainable manufacturing, enabling rapid prototyping, minimizing material waste, and reducing the carbon footprint associated with traditional methods. However, their reliance on fossil-based materials limits their broad application. This study presents a novel approach for developing a single-component, fully cellulosic, natural-based resin for 3D printing hydrogels using digital light processing (DLP). Cellulose was dissolved in an aqueous alkali/urea system and modified to obtain photopolymerizable derivatives. Two cellulose sources were used: Avicel® and cellulose pulp obtained from an industrial process. The single-polymer resins produced dimensionally stable, free-standing 3D objects with good resolution and shape fidelity. Despite the low polymer concentration (2.5 and 5 wt%), the cellulose resins exhibited fast curing kinetics, producing hydrogels with good mechanical properties, capable of withstanding compressive stress up to 135 kPa. Additionally, the printed hydrogels absorbed and retained large amounts of water (up to 427 %), while maintaining their shape and integrity in acidic and alkaline media. The hydrogels were stable to hydrolytic degradation, maintained their shape for up to four weeks, and were cytocompatible with fibroblast cells, indicating their potential for biomedical applications.

Keywords:  3D printing; Allyl cellulose; Digital light processing (DLP)

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.141389
bioRxiv. 2025 Feb 11. pii: 2025.02.04.636331. [Epub ahead of print]

Anti-resonance in developmental signaling regulates cell fate decisions.

Samuel J Rosen, Olivier Witteveen, Naomi Baxter, Ryan S Lach, Marianne Bauer, Maxwell Z Wilson.

Cells process dynamic signaling inputs to regulate fate decisions during development. While oscillations or waves in key developmental pathways, such as Wnt, have been widely observed, the principles governing how cells decode these signals remain unclear. By leveraging optogenetic control of the Wnt signaling pathway in both HEK293T cells and H9 human embryonic stem cells, we systematically map the relationship between signal frequency and downstream pathway activation. We find that cells exhibit a minimal response to Wnt at certain frequencies, a behavior we term anti-resonance. We developed both detailed biochemical and simplified hidden variable models that explain how anti-resonance emerges from the interplay between fast and slow pathway dynamics. Remarkably, we find that frequency directly influences cell fate decisions involved in human gastrulation; signals delivered at anti-resonant frequencies result in dramatically reduced mesoderm differentiation. Our work reveals a previously unknown mechanism of how cells decode dynamic signals and how anti-resonance may filter against spurious activation. These findings establish new insights into how cells decode dynamic signals with implications for tissue engineering, regenerative medicine, and cancer biology.

DOI: https://doi.org/10.1101/2025.02.04.636331
J Funct Biomater. 2025 Feb 18. pii: 69. [Epub ahead of print]16(2):

Schiff Base-Crosslinked Tetra-PEG-BSA Hydrogel: Design, Properties, and Multifunctional Functions.

Yuanyuan Qu, Jinlong Li, Xin Jia, Lijun Yin.

  Hydrogel network structures play a crucial role in determining mechanical properties and have broad applications in biomedical and industrial fields. Therefore, their rational design is essential. Herein, we developed a Schiff base-crosslinked hydrogel through the reaction of Tetra-armed polyethylene glycol with aldehyde end groups (Tetra-PEG-CHO) and bovine serum albumin (BSA) under alkaline conditions. In addition, the Tetra-PEG-BSA hydrogel showed a rapid gelation time of around 11 s, much faster than that of the GLU-BSA, HT-BSA, and GDL-BSA hydrogels. It had high optical transmittance (92.92% at 600 nm) and swelling ratios superior to the other gels in different solutions, maintaining structural integrity even in denaturing environments such as guanidine hydrochloride and SDS. Mechanical tests showed superior strain at break (84.12 ± 0.76%), rupture stress (28.64 ± 1.21 kPa), and energy dissipation ability (468.0 ± 34.9 kJ·m-3), surpassing all control group hydrogels. MTT cytotoxicity assays indicated that cell viability remained >80% at lower concentrations, confirming excellent biocompatibility. These findings suggest that Tetra-PEG-BSA hydrogels may serve as effective materials for drug delivery, tissue engineering, and 3D printing.

Keywords:  BSA; Schiff base; Tetra-PEG; hydrogel; protein

DOI:  https://doi.org/10.3390/jfb16020069
Chem Sci. 2025 Feb 25.

Photo-regulated disulfide crosslinking: a versatile approach to construct mucus-inspired hydrogels.

Rui Chen, Krishnendu Das, Jun Feng, Boonya Thongrom, Rainer Haag.

The remarkable defensive ability of native mucus against pathogens has encouraged scientists to map its structure--property correlation and its influence on immune defense mechanisms. However, its poorly defined structure, source-dependent composition, and low availability limit the usefulness of native mucus in the laboratory. This gap creates a strong demand for the development of synthetic mucus-mimetic materials. Here, we report a straightforward strategy for constructing mucus-mimetic hydrogels through photo-regulated disulfide crosslinking. Light-responsive 1,2-dithiolane attached to a linear polyglycerol sulfate (lPGS) backbone allows the macromolecular building blocks to crosslink and form the hydrogel, which mirrors the chemistry of native mucus hydrogel formation with its disulfide-linked mucin chains. The viscoelastic properties of the hydrogel can be easily tuned by controlling both the light exposure time and the number of 1,2-dithiolane units within the polymer backbone. Furthermore, localized UV irradiation allows for spatially resolved hydrogel formation. Importantly, this synthetic polymer can directly crosslink with native mucin, bovine submaxillary mucin (BSM), to convert it into a hydrogel at physiological pH. The versatility of this approach - hydrogel formation via photo-regulated disulfide crosslinking - can be used to develop a synthetic mucus model.

DOI: https://doi.org/10.1039/d4sc08284b
Adv Sci (Weinh). 2025 Feb 23. e2410903

A Novel Gene Synthesis Platform for Designing Functional Protein Polymers.

Toshimasa Homma, Rie Yamamoto, Lily Zuin Ping Ang, Alaa Fehaid, Mitsuhiro Ebara.

  Recombinant protein polymers with repeat sequences of specific amino acids can be regarded as sustainable functional materials that can be designed using genetic engineering. However, synthesizing genes encoding these proteins is significantly time-consuming and labor-intensive owing to the difficulty of using common gene synthesis tools, such as restriction enzymes and PCR primers. To overcome these obstacles, a novel method is proposed herein: seamless cloning of rolling-circle amplicons (SCRCA). This method involves one-pot preparation of repetitive-sequence genes with overlapping ends for cloning, facilitating the easy construction of the desired recombinants. SCRCA is used to synthesize 10 genes encoding hydrophilic resilin-like and hydrophobic elastin-like repeat units that induce liquid-liquid phase separation. SCRCA shows higher transformation efficiency and better workability than conventional methods, and the time and budget required for SCRCA are comparable to those required for non-repetitive-sequence gene synthesis. Additionally, SCRCA facilitates the construction of a repeat unit library at a low cost. The library shows considerably higher diversity than that of the current state-of-the-art method. By combining this library construction with the directed evolution concept, an elastin-like protein polymer with the desired functions can be rapidly developed. SCRCA can greatly accelerate research on protein polymers.

Keywords:  directed evolution; gene synthesis; protein polymers; repeat sequences; rolling‐circle amplification

DOI:  https://doi.org/10.1002/advs.202410903
Expert Opin Drug Deliv. 2025 Feb 25. 1-7

Injectable pulsatile drug delivery hydrogels: how do we get to the clinic?

Kayla Baker, Todd Hoare.



Keywords:  Hydrogel; clinical translation; drug delivery; on-demand; pulsatile release

DOI:  https://doi.org/10.1080/17425247.2025.2472001
Science. 2025 Feb 27. eadv9789

TIGR-Tas: A family of modular RNA-guided DNA-targeting systems in prokaryotes and their viruses.

Guilhem Faure, Makoto Saito, Max E Wilkinson, Natalia Quinones-Olvera, Peiyu Xu, Daniel Flam-Shepherd, Stephanie Kim, Nishith Reddy, Shiyou Zhu, Lilia Evgeniou, Eugene V Koonin, Rhiannon K Macrae, Feng Zhang.

RNA-guided systems provide remarkable versatility, enabling diverse biological functions. Through iterative structural and sequence homology-based mining starting with a guide RNA-interaction domain of Cas9, we identified a family of RNA-guided DNA-targeting proteins in phage and parasitic bacteria. Each system consists of a Tandem Interspaced Guide RNA (TIGR) array and a TIGR-associated (Tas) protein containing a Nop domain, sometimes fused to HNH (TasH) or RuvC (TasR) nuclease domains. We show that TIGR arrays are processed into 36-nt RNAs (tigRNAs) that direct sequence-specific DNA binding through a tandem-spacer targeting mechanism. TasR can be reprogrammed for precise DNA cleavage, including in human cells. The structure of TasR reveals striking similarities to box C/D snoRNPs and IS110 RNA-guided transposases, providing insights into the evolution of diverse RNA-guided systems.

DOI: https://doi.org/10.1126/science.adv9789
Nat Chem. 2025 Feb 26.

A glycan foldamer that uses carbohydrate-aromatic interactions to perform catalysis.

Kaimeng Liu, Martina Delbianco.

In nature, the ability to catalyse reactions is primarily associated with proteins and ribozymes. Inspired by these systems, peptide-based catalysts have been designed to accelerate chemical reactions and/or ensure regio- and stereoselective transformations. We wondered whether other biomolecules (such as glycans) could be designed to perform catalytic functions, expanding the portfolio of synthetic functional oligomers. Here we report a glycan foldamer inspired by the natural Sialyl Lewis X antigen that acts as catalyst in a chemical reaction. This glycan-based catalyst benefits from structural rigidity and modular adaptability, incorporating a substrate-recognition motif alongside a catalytic active site. Leveraging the inherent ability of carbohydrates to engage in CH-π interactions with aromatic substrates, we demonstrate the recruitment and functionalization of a tryptophan via a Pictet-Spengler transformation. Our modular glycan catalyst accelerates the reaction kinetics, enabling the modification of tryptophan-containing peptides in aqueous environments. Our findings pave the way for the development of glycan-based catalysts and suggest the possibility of catalytic capabilities of glycans in biological contexts.

DOI: https://doi.org/10.1038/s41557-025-01763-6
Mater Horiz. 2025 Feb 28.

Droplet-templating soft materials into structured bead-based aerogels with compartmentalized or welded configurations.

Shayan Ghasemi, Mahyar Panahi-Sarmad, Elnaz Erfanian, Tianyu Guo, Vahid Rad, Adel Jalaee, Gabriel Banvillet, E Johan Foster, Kam C Tam, Masoud Soroush, Feng Jiang, Orlando J Rojas, Milad Kamkar.

Achieving precise control over the composition and architecture of nanomaterial-based aerogels remains a significant challenge. Here, we introduce a droplet-templating approach to engineer ultra-lightweight aerogels via the interfacial co-assembly of nanoparticles-surfactants (NPSs) at polar/apolar liquid interfaces. This approach enables the creation of aerogels with tailored compartmentalized or welded bead architectures, exhibiting multilayer, gradient, and hybrid morphologies from a range of 1D and 2D nanomaterials. By precisely controlling evaporation and freeze-drying processes, we fabricate aerogels with customizable micro-domains, without requiring chemical binders. Our approach provides a platform for developing soft materials with tunable properties, paving a new path for applications in soft matter and aerogel engineering.

DOI: https://doi.org/10.1039/d4mh01896f
ACS Appl Mater Interfaces. 2025 Feb 27.

Dual-Functional Antimicrobial and Low-Fouling Cellulose Coatings.

Sandya S A Athukoralalage, Zane Datson, Nadim Darwish, Yanshan Zhu, Ka H K Chung, Keng Chew, Alan E Rowan, Nasim Amiralian.

  Surfaces contaminated with pathogens raise significant concerns due to their potential role in increasing the risk of disease transmission and subsequent infection. Existing surface coatings face several challenges that undermine their effectiveness and their broader applicability. These include the impact of surface topography on pathogen adhesion, which leads to biofouling, high production costs, scalability issues, as well as environmental concerns stemming from the utilization of toxic antifoulants and biocides. Here, we report dual-functional surface coatings with intrinsic antimicrobial and low fouling properties that are synergistic. The coatings are a porous reactive cellulose fibers network with dialdehyde functionality that demonstrates high antibacterial and antiviral performance against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Escherichia coli, and influenza A/H1N1 virus. Furthermore, we showed that the wettability of the coating significantly reduces the adhesion and colony formation of bacteria and their dead debris after inactivation by dialdehyde groups. The reactive cellulose fibers did not demonstrate any acute toxicity on L929 cells, which can meet the safe use of coating on the contact surfaces. The cellulose fibers coating derived from agricultural waste is cost-effective, eco-friendly, and highly scalable and is promising for use in packaging, household products, public facilities, and medical settings surfaces.

Keywords:  antimicrobial; antitransmission materials; antiviral coating; biofouling; dual-functional materials; nanocellulose; pathogen transmission

DOI:  https://doi.org/10.1021/acsami.4c21252
Proc Natl Acad Sci U S A. 2025 Mar 04. 122(9): e2424124122

Multiscale toughening mechanisms in biomimetic tendon-like hydrogels.

Xiao Guo, Xinyu Dong, Guijin Zou, Haoqi Zhang, Kaiyang Zeng, Huajian Gao, Wei Zhai.

  Mimicking hierarchical structures found in nature, such as nacre and tendon, has led to remarkable successes in the creation of biomimetic materials with exceptional properties. The depth of knowledge derived from nature extends far beyond mere trial-and-error fabrication by providing deep insights into the toughening mechanisms that are integral to natural materials. A key challenge is understanding how these toughening mechanisms can be effectively translated into biomimetic materials. Here, we characterize the multiscale mechanical behavior of tendon-like fibrous hydrogels, unraveling the intricate toughening mechanisms at play across multiple scales-from dynamic molecular interactions and nanoscale fibril sliding, to anisotropic microscale characteristics and macroscopic performance-using a combination of experimental and simulation approaches. Additionally, we address the open question of how hierarchical structures exhibit mechanical properties at different scales, demonstrating that hydrogels, fibrils, and chains take up successively lower levels of strain in a ratio of 11.5:3.2:2. This work establishes a comprehensive framework for exploring nature-inspired materials, marking a significant step forward in the advancement of biomimetic technology.

Keywords:  biomimetic hydrogel; mechanical behavior; multiscale characterization; toughening mechanisms

DOI:  https://doi.org/10.1073/pnas.2424124122
Adv Mater. 2025 Feb 28. e2414692

Development of Bioorthogonally Degradable Tough Hydrogels Using Enamine N-Oxide Based Crosslinkers.

Thomas T Kim, Deep Malu, Dongjing He, Yuhang Hu, Justin Kim.

  Inducibly degradable polymers present new opportunities to integrate tough hydrogels into a wide range of biomaterials. Rapid and inducible degradation enables fast transition in material properties without sacrificing material integrity prior to removal. In pursuit of bioorthogonal chemical modalities that will enable inducible polymer degradation in biologically relevant environments, enamine N-oxide crosslinkers are developed for double network acrylamide-based polymer/alginate hydrogels. Bioorthogonal dissociation initiated by the application of aqueous diboron solution through several delivery mechanisms effectively lead to polymer degradation. Their degradation by aqueous B2(OH)4 solution results in a fracture energy half-life of <10 min. The biocompatibility of the degradable hydrogels and B2(OH)4 reagent is assessed, and the removability of strongly adhered tough hydrogels on mice skin is evaluated. Thermoresponsive PNiPAAm/Alg hydrogels are fabricated and application of the hydrogels as a chemically inducible degradable intraoral wound dressing is demonstrated. It is demonstrated through in vivo maximum tolerated dose studies that diboron solution administered to mice by oral gavage is well tolerated. Successful integration of enamine N-oxides within the tough double network hydrogels as chemically degradable motifs demonstrates the applicability of enamine N-oxides in the realm of polymer chemistry and highlights the importance of chemically induced bioorthogonal dissociation reactions for materials science.

Keywords:  bioorthogonal; degradable; double network hydrogels; enamine N‐oxides; intraoral wound dressings; tough hydrogels

DOI:  https://doi.org/10.1002/adma.202414692
ACS Appl Mater Interfaces. 2025 Feb 27.

DNA Origami Barcodes for Immunostaining.

Praneetha Sundar Prakash, Foram M Joshi, Eric Vogelsberg, Glenn A O Cremers, Fatih N Gür, Yusuke Sato, Tom F A de Greef, Marius Ader, Thomas Kurth, Diana Patricia Nunes Gonçalves, Thorsten L Schmidt.

  In histology, immunostaining of biological samples is a gold standard for studying cellular processes, such as the expression of cell surface markers or the cellular uptake of proteins and drug molecules. Immuno-gold labeling is a commonly used technique to achieve nanometer spatial resolution, but simultaneous visualization of multiple antigens in parallel is an unresolved challenge. Herein, we demonstrate a DNA nanotechnology-based approach to label antigens in transmission electron microscopy images of tissue sections with high contrast patterns. For this, we attached gold nanoparticles to designated binding positions on DNA origami structures that act as visual "barcodes." These barcodes are then hybridized to complementary strands of DNA-modified antibodies that are bound to their respective antigens on ultrathin tissue resin sections. As a proof of concept, we demonstrate several types of barcodes and two different antibody labeling techniques that will expand the multiplexing abilities of immunostaining in a highly modular way.

Keywords:  DNA origami; bioconjugation; electron microscopy; immunostaining; multiplexing; structural DNA nanotechnology

DOI:  https://doi.org/10.1021/acsami.4c19153
Proc Natl Acad Sci U S A. 2025 Mar 04. 122(9): e2422085122

Directed evolution of a sequence-specific covalent protein tag for RNA labeling.

Rongbing Huang, Alice Y Ting.

  Efficient methods for conjugating proteins to RNA are needed for RNA delivery, imaging, editing, interactome mapping, and barcoding applications. Noncovalent coupling strategies using viral RNA binding proteins such as MS2/MCP have been widely applied but are limited by tag size, sensitivity, and dissociation over time. We took inspiration from a sequence-specific, covalent protein-DNA conjugation method based on the Rep nickase of a porcine circovirus called "HUH tag". Though wild-type HUH protein has no detectable activity toward an RNA probe, we engineered an RNA-reactive variant, called "rHUH", through 7 generations of yeast display-based directed evolution. Our 13.4 kD rHUH has 12 mutations relative to HUH and forms a covalent tyrosine-phosphate ester linkage with a 10-nucleotide RNA recognition sequence ("rRS") within minutes. We engineered the sensitivity down to 1 nM of target RNA, shifted the metal ion requirement from Mn2+ toward Mg2+, and demonstrated efficient labeling in mammalian cell lysate. This work paves the way toward a potentially powerful methodology for sequence-specific covalent protein-RNA conjugation in biological systems.

Keywords:  RNA conjugation; RNA technology; RNA–protein interactions; directed evolution; protein engineering

DOI:  https://doi.org/10.1073/pnas.2422085122
ACS Nano. 2025 Feb 25.

A Self-Driving Lab for Nano- and Advanced Materials Synthesis.

Mohammad Zaki, Carsten Prinz, Bastian Ruehle.

  The recent emergence of self-driving laboratories (SDL) and material acceleration platforms (MAPs) demonstrates the ability of these systems to change the way chemistry and material syntheses will be performed in the future. Especially in conjunction with nano- and advanced materials which are generally recognized for their great potential in solving current material science challenges, such systems can make disrupting contributions. Here, we describe in detail MINERVA, an SDL specifically built and designed for the synthesis, purification, and in line characterization of nano- and advanced materials. By fully automating these three process steps for seven different materials from five representative, completely different classes of nano- and advanced materials (metal, metal oxide, silica, metal organic framework, and core-shell particles) that follow different reaction mechanisms, we demonstrate the great versatility and flexibility of the platform. We further study the reproducibility and particle size distributions of these seven representative materials in depth and show the excellent performance of the platform when synthesizing these material classes. Lastly, we discuss the design considerations as well as the hardware and software components that went into building the platform and make all of the components publicly available.

Keywords:  Self-driving laboratories; advanced materials; automation; in-line characterization; materials acceleration platforms; nanomaterials; robotics

DOI:  https://doi.org/10.1021/acsnano.4c17504
AIChE J. 2024 Feb;pii: e18307. [Epub ahead of print]70(2):

Nanoparticle transport in biomimetic polymer-linked emulsions.

Daniel P Keane, Colby J Constantine, Matthew D Mellor, Ryan Poling-Skutvik.

  The ability of nanoparticles to penetrate and transport through soft tissues is essential to delivering therapeutics to treat diseases or signaling agents for advanced imaging and sensing. Nanoparticle transport in biological systems, however, is challenging to predict and control due to the physicochemical complexity of tissues and biological fluids. Here, we demonstrate that nanoparticles suspended in a novel class of soft matter-polymer-linked emulsions (PLEs)-exhibit characteristics essential for mimicking transport in biological systems, including subdiffusive dynamics, non-Gaussian displacement distributions, and decoupling of dynamics from material viscoelasticity. Using multiple particle tracking, we identify the physical mechanisms underlying this behavior, which we attribute to a coupling of nanoparticle dynamics to fluctuations in the local network of polymer-linked droplets. Our findings demonstrate the potential of PLEs to serve as fully synthetic mimics of biological transport.

Keywords:  complex fluids; diffusion; microrheology; transport

DOI:  https://doi.org/10.1002/aic.18307
J Am Chem Soc. 2025 Feb 27.

Functional Design of Peptide Materials Based on Supramolecular Cohesion.

Simon A Egner, Mayank Agrawal, Hiroaki Sai, Michael D Dore, Liam C Palmer, Samuel I Stupp.

Peptide materials offer a broad platform to design biomimetic soft matter, and filamentous networks that emulate those in extracellular matrices and the cytoskeleton are among the important targets. Given the vast sequence space, a combination of computational approaches and readily accessible experimental techniques is required to design peptide materials efficiently. We report here on a strategy that utilizes this combination to predict supramolecular cohesion within filaments of peptide amphiphiles, a property recently linked to supramolecular dynamics and consequently bioactivity. Using established coarse-grained simulations on 10,000 randomly generated peptide sequences, we identified 3500 likely to self-assemble in water into nanoscale filaments. Atomistic simulations of small clusters were used to further analyze this subset of sequences and identify mathematical descriptors that are predictive of intermolecular cohesion, which was the main purpose of this work. We arbitrarily selected a small cohort of these sequences for chemical synthesis and verified their fiber morphology. With further characterization, we were able to link the latent heat associated with fiber to micelle transitions, an indicator of cohesion and potential supramolecular dynamicity within the filaments, to calculated hydrogen bond densities in the simulation clusters. Based on validation from in situ synchrotron X-ray scattering and differential scanning calorimetry, we conclude that the phase transitions can be easily observed by very simple polarized light microscopy experiments. We are encouraged by the methodology explored here as a relatively low-cost and fast way to design potential functions of peptide materials.

DOI: https://doi.org/10.1021/jacs.4c17867