ArticleProceedings of the National Academy of Sciences of the United States of America2022
Aging can transform single-component protein condensates into multiphase architectures.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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64 citing papers in PubMed.
- Biomolecular coacervation-mediated materials: Phase states, phase transitions, and biomedical applications.Bioactive materials · 2027Review
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- Cooperative molecular interaction networks govern PARP1 inhibitor selectivity and binding affinity.PLoS computational biology · 2026Article
- Computational rheometry for modeling viscoelasticity and mechanical responses of biomolecular condensates.Biophysical journal · 2026Article
- Nonequilibrium phases of a biomolecular condensate facilitated by enzyme activity.Soft matter · 2026Article
- Two-Nanosensor Electrochemical Profiling of Catecholamine Vesicle Interactions With Acute and Chronic Stress Granules in Living Cells.Angewandte Chemie (International ed. in English) · 2026Article
- Determination of Nucleotide-Nucleotide and Nucleotide-Amino Acid Binding Interactions from All-Atom Potential-of-Mean-Force Calculations.ACS physical chemistry Au · 2026Article
- Role of p62 nuclear condensates in regulating ubiquitin-mediated proteasomal degradation.Essays in biochemistry · 2025Review
- Biomolecular condensate microstructure is invariant to sequence-encoded molecular and macroscopic properties.Soft matter · 2025Article
- Molecular insights on the mechanism of α1-antitrypsin condensate formation and maturation.PLoS computational biology · 2025Article
- Dissecting the Molecular Determinants of α-synuclein Phase Separation and Condensate Aging: The Pivotal Role of β-Sheet-Rich Motifs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Intrinsically Disordered Protein Coating for Oral Delivery of Peptide Drugs.bioRxiv : the preprint server for biology · 2025Article
- A Hybrid UA-CG Force Field for Aggregation Simulation of Amyloidogenic Peptide via Liquid-like Intermediates.Molecules (Basel, Switzerland) · 2025Article
- In situ secondary structure imaging of protein phase separation and aggregation by hyperspectral stimulated Raman scattering microscopy.Nature communications · 2025Article
- Charged peptides enriched in aromatic residues decelerate condensate ageing driven by cross-β-sheet formation.Nature communications · 2025Article
- Computational rheometry of viscoelastic networks: From random graphs to biomolecular condensates.bioRxiv : the preprint server for biology · 2025Article
- Time-dependent catalytic activity in aging condensates.Nature communications · 2025Article
- Biomolecular condensate microstructure couples molecular and mesoscale properties.bioRxiv : the preprint server for biology · 2025Article
- Emergent mechanics of a networked multivalent protein condensate.Nature communications · 2025Article
4 more citing papers are in PubMed but not listed here.
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7 authors.
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Abstract
Phase-separated biomolecular condensates that contain multiple coexisting phases are widespread in vitro and in cells. Multiphase condensates emerge readily within multicomponent mixtures of biomolecules (e.g., proteins and nucleic acids) when the different components present sufficient physicochemical diversity (e.g., in intermolecular forces, structure, and chemical composition) to sustain separate coexisting phases. Because such diversity is highly coupled to the solution conditions (e.g., temperature, pH, salt, composition), it can manifest itself immediately from the nucleation and growth stages of condensate formation, develop spontaneously due to external stimuli or emerge progressively as the condensates age. Here, we investigate thermodynamic factors that can explain the progressive intrinsic transformation of single-component condensates into multiphase architectures during the nonequilibrium process of aging. We develop a multiscale model that integrates atomistic simulations of proteins, sequence-dependent coarse-grained simulations of condensates, and a minimal model of dynamically aging condensates with nonconservative intermolecular forces. Our nonequilibrium simulations of condensate aging predict that single-component condensates that are initially homogeneous and liquid like can transform into gel-core/liquid-shell or liquid-core/gel-shell multiphase condensates as they age due to gradual and irreversible enhancement of interprotein interactions. The type of multiphase architecture is determined by the aging mechanism, the molecular organization of the gel and liquid phases, and the chemical makeup of the protein. Notably, we predict that interprotein disorder to order transitions within the prion-like domains of intracellular proteins can lead to the required nonconservative enhancement of intermolecular interactions. Our study, therefore, predicts a potential mechanism by which the nonequilibrium process of aging results in single-component multiphase condensates.
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