ArticleNature physics2024
Sequence-specific interactions determine viscoelasticity and aging dynamics of protein condensates.
Article in Nature physics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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97 citing papers in PubMed.
- Progress toward linking single-molecule behavior and condensate material properties.Current opinion in structural biology · 2026Review
- Article
- Multiscale physical effects of CpG methylation on DNA mechanics, nucleosome wrapping, and chromatin condensates.EMBO reports · 2026Article
- Designed IDPs phase separate and mix or demix according to sequence designed parameters.bioRxiv : the preprint server for biology · 2026Article
- Deletion Analysis of Phase Separation, Amyloid Formation and Prion Propagation by the Intrinsically Disordered Region of Yeast Sup35 Protein.International journal of molecular sciences · 2026Article
- Biomolecular condensates can function as inherent catalysts.Molecular cell · 2026Article
- Dynamic Arrest and Tunable Gelation of Immunogenically Inert POEGMA Nanoparticles.ACS polymers Au · 2026Article
- Inhibition and Formation of Amyloid Fibrils in the Bulk and at the Interface of Biomolecular Condensates.Angewandte Chemie (International ed. in English) · 2026Review
- Valency-Limited Molecular Dynamics Simulations of Stickers-and-Spacers Polymers Reveal a Tradeoff Between Condensation and Organization.bioRxiv : the preprint server for biology · 2026Article
- Phase separation across membranes and condensates in cell organization and function.Nature reviews. Molecular cell biology · 2026Review
- The emerging synergy of experimental and computational approaches for therapeutic modulation of biomolecular condensates.SLAS discovery : advancing life sciences R & D · 2026Review
- Multiscale Architecture and Mechanics of the Cell Nucleus: Implications for Disease, Bioengineering and Nanomedicine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Interplay of Noncovalent Interactions in Phase Separation Mediated by Tyrosine-Rich and Arginine-Rich Polypeptides.Journal of the American Chemical Society · 2026Article
- MOFF2: A Transferable Coarse-Grained Protein Force Field for Predictive Condensate Simulations.bioRxiv : the preprint server for biology · 2026Article
- Distinguishing near- versus off-critical phase behaviors of intrinsically disordered proteins.Reports on progress in physics. Physical Society (Great Britain) · 2026Article
- Kinetics and Spatial Distribution of β-Sheet Development in TDP-43ACS chemical neuroscience · 2026Article
- Molecular determinants of arginine versus lysine cation-π interactions in biomolecular condensates.Communications chemistry · 2026Article
- Intrinsically disordered protein coating for oral delivery of peptide drugs.Cell biomaterials · 2026Article
- Developing Design Rules for Polyelectrolyte Complex Materials: Role of Polyelectrolyte Length, Charged Group, and Backbone.Macromolecules · 2026Article
- Computational rheometry for modeling viscoelasticity and mechanical responses of biomolecular condensates.Biophysical journal · 2026Article
37 more citing papers are in PubMed but not listed here.
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12 authors.
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Abstract
Biomolecular condensates are viscoelastic materials. Here, we investigate the determinants of sequence-encoded and age-dependent viscoelasticity of condensates formed by the prion-like low-complexity domain of the protein hnRNP A1 and its designed variants. We find that the dominantly viscous forms of the condensates are metastable Maxwell fluids. A Rouse-Zimm model that accounts for the network-like organization of proteins within condensates reproduces the measured viscoelastic moduli. We show that the strengths of aromatic inter-sticker interactions determine sequence-specific amplitudes of elastic and viscous moduli, and the timescales over which elastic properties dominate. These condensates undergo physical ageing on sequence-specific timescales. This is driven by mutations to spacer residues that weaken the metastability of dominantly viscous phases. The ageing of condensates is accompanied by disorder-to-order transitions, leading to the formation of non-fibrillar, beta-sheet-containing, semi-crystalline, elastic, Kelvin-Voigt solids. Our results suggest that sequence grammars, which refer to amino acid identities of stickers versus spacers in prion-like low-complexity domains, have evolved to afford control over metastabilities of dominantly viscous fluid phases of condensates. This selection is likely to render barriers for conversion from metastable fluids to globally stable solids insurmountable on functionally relevant timescales.
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