ArticleProceedings of the National Academy of Sciences of the United States of America2021
Ligand effects on phase separation of multivalent macromolecules.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 165 citations in OpenAlex.
- Article
- Holographic Fingerprinting Reveals Oligomer-Driven Phase Separation in Bovine Serum Albumin.Chemical & biomedical imaging · 2026Article
- Artificial intelligence and ultra-high performance computing methods and experiments for drug discovery: virtual screening, deep learning, molecular dynamics simulations, ADMET modelling, and experimental validation.Molecular biomedicine · 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
- Homer condensates orchestrate YAP-Wnt signaling crosstalk downstream of the Crumbs polarity complex.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- AI-discovered protein fragments as generalizable regulators of biomolecular condensates.bioRxiv : the preprint server for biology · 2026Article
- Conformational landscapes resolved by ion mobility mass spectrometry reveal mechanisms of polyubiquitin-controlled phase separation.Chemical science · 2026Article
- Short autoinhibitory sequences control phase separation of an essential bacterial transcription termination factor.The EMBO journal · 2026Article
- Liquid-liquid phase separation-driven regulated cell death: from molecular mechanisms to therapeutic strategies.Cell death discovery · 2026Review
- Programmable Coacervates Based on Minimalist Sticker-Spacer Frameworks: Chemical Design, Functions, and Emerging Applications.ACS applied materials & interfaces · 2026Review
- Cell flocculation and phase-separation support macro-scale tissue slab construction in a scaffold-free manner.Materials today. Bio · 2026Article
- Article
- Nuclear-import receptors remodel the dilute phase to suppress phase transitions of RNA-binding proteins with prion-like domains.bioRxiv : the preprint server for biology · 2025Article
- Lipid-Mediated Assembly of Biomolecular Condensates: Mechanisms, Regulation, and Therapeutic Implications.Biology · 2025Review
- Biomolecular phase separation in tumorigenesis: from aberrant condensates to therapeutic vulnerabilities.Molecular cancer · 2025Review
- Xist condensates: perspectives for therapeutic intervention.Genome biology · 2025Review
- Mineralocorticoid receptor phase separation modulates cardiac preservation.Nature cardiovascular research · 2025Article
- Active transport enables protein condensation in cells.Science advances · 2025Article
- Modular in vivo assembly of Arabidopsis FCA oligomers into condensates competent for RNA 3' processing.The EMBO journal · 2025Article
- Genetically-Encoded Phase Separation Sensors Enable High-Fidelity Live-Cell Probing of Biomolecular Condensates.ACS sensors · 2025Article
35 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Biomolecular condensates enable spatial and temporal control over cellular processes by concentrating biomolecules into nonstoichiometric assemblies. Many condensates form via reversible phase transitions of condensate-specific multivalent macromolecules known as scaffolds. Phase transitions of scaffolds can be regulated by changing the concentrations of ligands, which are defined as nonscaffold molecules that bind to specific sites on scaffolds. Here, we use theory and computation to uncover rules that underlie ligand-mediated control over scaffold phase behavior. We use the stickers-and-spacers model wherein reversible noncovalent cross-links among stickers drive phase transitions of scaffolds, and spacers modulate the driving forces for phase transitions. We find that the modulatory effects of ligands are governed by the valence of ligands, whether they bind directly to stickers versus spacers, and the relative affinities of ligand-scaffold versus scaffold-scaffold interactions. In general, all ligands have a diluting effect on the concentration of scaffolds within condensates. Whereas monovalent ligands destabilize condensates, multivalent ligands can stabilize condensates by binding directly to spacers or destabilize condensates by binding directly to stickers. Bipartite ligands that bind to stickers and spacers can alter the structural organization of scaffold molecules within condensates even when they have a null effect on condensate stability. Our work highlights the importance of measuring dilute phase concentrations of scaffolds as a function of ligand concentration in cells. This can reveal whether ligands modulate scaffold phase behavior by enabling or suppressing phase separation at endogenous levels, thereby regulating the formation and dissolution of condensates in vivo.
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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 OpenQuestion graph.