Single-fluorogen imaging reveals distinct environmental and structural features of biomolecular condensates
Year: 2025
Type: article
Abstract: Biomolecular condensates are viscoelastic materials. Simulations predict that condensates formed by intrinsically disordered proteins are network fluids defined by spatially inhomogeneous organization of the underlying molecules. Here, we test these predictions and find that molecules within condensates are organized into slow-moving nanoscale clusters and fast-moving dispersed molecules. These results, obtained using single-fluorogen tracking and super-resolution imaging of different disordered protein-based condensates, affirm the predicted spatially inhomogeneous organization of molecules within condensates. We map the internal environments and interfaces of condensates using fluorogens that localize differently to the interiors versus interface between dilute phase and condensate. We show that nanoscale clusters within condensates are more hydrophobic than regions outside the clusters, and regions within condensates that lie outside clusters are more hydrophobic than coexisting dilute phases. Our findings provide a structural and dynamical basis for the viscoelasticity of condensates.
Source: Nature Physics
Institution: Washington University in St. Louis
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Awards: G1330966717, G2103874293, (MURI-20) UNCOVERING AND APPLYING THE INTERFACIAL DESIGN PRINCIPLES OF MULTIPHASIC NATURAL AND SYNTHETIC ORGANELLES, G4769724255, Six-Dimensional Single-Molecule Nanoscopy for Elucidating the Dynamic Organization of Biomolecules, Understanding the sequence and structural determinants of phase behavior of ALS-causing proteins, G966951788
OpenAlex ID: W4408467080
