ArticleProceedings of the National Academy of Sciences of the United States of America2024
De novo design of modular protein hydrogels with programmable intra- and extracellular viscoelasticity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 51 citations in OpenAlex.
- Artificial intelligence-assisted design of self-assembling peptide hydrogels for neural regeneration: Principles and opportunities.Bioactive materials · 2027Review
- Construction of a dual-compartment hydrogel by protein-based triblock copolymer for theMaterials today. Bio · 2026Article
- Microscale Mechanical Cues in Hydrogels: Engineering Strategies to Modulate Cell Fates in Three Dimensions.Cell biomaterials · 2026Article
- Engineering complexity into protein-based biomaterials for biomedical applications.Nature reviews. Materials · 2026Article
- Computational design of superstable proteins through maximized hydrogen bonding.Nature chemistry · 2026Article
- Stimuli-triggered formation ofCell biomaterials · 2026Article
- Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026Review
- De novo design of light-responsive protein-protein interactions enables reversible formation of protein assemblies.Nature chemistry · 2025Article
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- Bond-centric modular design of protein assemblies.Nature materials · 2025Article
- Extracellular Matrix Viscoelasticity: A Dynamic Regulator of Cellular Behavior.Annals of biomedical engineering · 2025Review
- PhoCoil: A photodegradable and injectable single-component recombinant protein hydrogel for minimally invasive delivery and degradation.Science advances · 2025Article
- Article
- Employing the SpyTag-SpyCatcher Reaction for the Modification of Supramolecular Polymers with Functional Proteins.Bioconjugate chemistry · 2025Article
- Leveraging Protein-Ligand and DNA Interactions to Control Hydrogel Mechanics.Journal of the American Chemical Society · 2025Article
- Self-Assembling Peptide-Co-PPIX Complex Catalyzes Photocatalytic Hydrogen Evolution and Forms Hydrogels.Molecules (Basel, Switzerland) · 2025Article
- Engineered Protein Hydrogels as Biomimetic Cellular Scaffolds.Advanced materials (Deerfield Beach, Fla.) · 2024Review
- Advancing Synthetic Hydrogels through Nature-Inspired Materials Chemistry.Advanced materials (Deerfield Beach, Fla.) · 2024Review
- Genetically Encoded XTEN-based Hydrogels with Tunable Viscoelasticity and Biodegradability for Injectable Cell Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
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14 authors at 4 institutions in 1 country.
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Abstract
Relating the macroscopic properties of protein-based materials to their underlying component microstructure is an outstanding challenge. Here, we exploit computational design to specify the size, flexibility, and valency of de novo protein building blocks, as well as the interaction dynamics between them, to investigate how molecular parameters govern the macroscopic viscoelasticity of the resultant protein hydrogels. We construct gel systems from pairs of symmetric protein homo-oligomers, each comprising 2, 5, 24, or 120 individual protein components, that are crosslinked either physically or covalently into idealized step-growth biopolymer networks. Through rheological assessment, we find that the covalent linkage of multifunctional precursors yields hydrogels whose viscoelasticity depends on the crosslink length between the constituent building blocks. In contrast, reversibly crosslinking the homo-oligomeric components with a computationally designed heterodimer results in viscoelastic biomaterials exhibiting fluid-like properties under rest and low shear, but solid-like behavior at higher frequencies. Exploiting the unique genetic encodability of these materials, we demonstrate the assembly of protein networks within living mammalian cells and show via fluorescence recovery after photobleaching (FRAP) that mechanical properties can be tuned intracellularly in a manner similar to formulations formed extracellularly. We anticipate that the ability to modularly construct and systematically program the viscoelastic properties of designer protein-based materials could have broad utility in biomedicine, with applications in tissue engineering, therapeutic delivery, and synthetic biology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.