ArticleBiophysical journal2021
The key role of solvent in condensation: Mapping water in liquid-liquid phase-separated FUS.
Article in Biophysical journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 136 citations in OpenAlex.
- Seeing the Chemistry of Biomolecular Condensates: In Situ Mapping of Composition and Water Content.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Chain collapse, reduced dielectric, and water release drive protein phase separation.Biophysical journal · 2026Article
- Article
- Enhanced Condensation of RNA Repeats Induced by Terahertz Oscillatory Fields.Molecules (Basel, Switzerland) · 2026Article
- Lipid Composition Modulates Secondary Structure at the Biocondensate-Membrane Interface.bioRxiv : the preprint server for biology · 2026Article
- Nucleation Kinetics Reveals a Distinct Biological Function Space of Biomolecular Condensates.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Origin of the ionic-strength dependent reentrant behavior in the liquid-liquid phase separation of uncharged intrinsically disordered proteins.Communications chemistry · 2026Article
- Navigating condensate micropolarity to enhance small-molecule drug targeting.Nature chemical biology · 2026Article
- FUS nanoclusters are a distinct state within the dilute phase.Nature communications · 2025Article
- Direct Optical Quantification of Chain Collapse, Reduced Dielectric, and Water Release Driving Protein Phase Separation.bioRxiv : the preprint server for biology · 2025Article
- Ultrafast Intermolecular Dynamics of Nanoconfined Water in Swollen Lipid Cubic Mesophases.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Role of Charge Patterning and Hydrophobicity in Peptide-Based Complex Coacervates.Biomacromolecules · 2025Article
- In situ secondary structure imaging of protein phase separation and aggregation by hyperspectral stimulated Raman scattering microscopy.Nature communications · 2025Article
- Beyond Electrostatic Interactions: H-Bond Dynamics in Arginine- versus Lysine-Rich Biocondensates.The journal of physical chemistry letters · 2025Article
- The Origin of the Ionic-strength Dependent Reentrant Behavior in Liquid-Liquid Phase Separation of Uncharged IDPs.bioRxiv : the preprint server for biology · 2025Article
- Terahertz calorimetry spotlights the role of water in biological processes.Nature reviews. Chemistry · 2025Review
- Engineering Protein-Polyelectrolyte Interactions for Cellular Applications.Annual review of chemical and biomolecular engineering · 2025Review
- Protein Crowding Effects on Hydration Water Dynamics.The journal of physical chemistry letters · 2025Article
- Structured protein domains enter the spotlight: modulators of biomolecular condensate form and function.Trends in biochemical sciences · 2025Review
- Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Formation of biomolecular condensates through liquid-liquid phase separation (LLPS) has emerged as a pervasive principle in cell biology, allowing compartmentalization and spatiotemporal regulation of dynamic cellular processes. Proteins that form condensates under physiological conditions often contain intrinsically disordered regions with low-complexity domains. Among them, the RNA-binding proteins FUS and TDP-43 have been a focus of intense investigation because aberrant condensation and aggregation of these proteins is linked to neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal dementia. LLPS occurs when protein-rich condensates form surrounded by a dilute aqueous solution. LLPS is per se entropically unfavorable. Energetically favorable multivalent protein-protein interactions are one important aspect to offset entropic costs. Another proposed aspect is the release of entropically unfavorable preordered hydration water into the bulk. We used attenuated total reflection spectroscopy in the terahertz frequency range to characterize the changes in the hydrogen bonding network accompanying the FUS enrichment in liquid-liquid phase-separated droplets to provide experimental evidence for the key role of the solvent as a thermodynamic driving force. The FUS concentration inside LLPS droplets was determined to be increased to 2.0 mM independent of the initial protein concentration (5 or 10 μM solutions) by fluorescence measurements. With terahertz spectroscopy, we revealed a dewetting of hydrophobic side chains in phase-separated FUS. Thus, the release of entropically unfavorable water populations into the bulk goes hand in hand with enthalpically favorable protein-protein interaction. Both changes are energetically favorable, and our study shows that both contribute to the thermodynamic driving force in phase separation.
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