Biomolecular condensates provide a unique environment for redox-mediated protein crosslinking
Year: 2026
Type: preprint
Abstract: Biomolecular condensates, often formed through liquid-liquid phase separation, are dynamic cellular compartments. Here, we demonstrate that a wide range of fluorescently tagged proteins undergo inadvertent, condensate-mediated crosslinking, resulting in rapid solidification of condensates under common fluorescence imaging conditions. The process is driven by excitation-induced, short-lived reactive oxygen species (ROS), whose otherwise limited crosslinking potential becomes uniquely enabled in the dense phase. In live cells, excitation-induced ROS potently trigger stress granule formation, while the ROS-driven solidification of condensates is modulated by compartment-dependent antioxidant buffering. Our findings demonstrate that condensates create a distinct environment that enables ROS chemistry unlikely to occur in the bulk cytosol. Furthermore, the cellular redox level can be a general regulator of condensate rheology. Beyond biological insights, our findings underscore the need for scrutiny when examining fluorophore-labeled condensates.
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: G1060533572, Integrative NMR and biophysical studies of fibrillar protein assemblies in health and disease, CAREER: Towards understanding mechanical signaling at the cell membrane, CAREER: Surfactant Proteins that Stabilize Biomolecular Condensates: From Biophysics to Biomaterials for Biomanufacturing, G8912969111, G9000159434, Understanding the viscoelasticity, surface tension, and membrane interactions of biomolecular condensates in live cells
OpenAlex ID: W7154563182