Biomolecular condensates form spatially inhomogeneous network fluids

Abstract

AbstractThe functions of biomolecular condensates are thought to be influenced by their material properties, and these are in turn determined by the multiscale structural features within condensates. However, structural characterizations of condensates are challenging, and hence rarely reported. Here, we deploy a combination of small angle neutron scattering, fluorescence recovery after photobleaching, and bespoke coarse-grained molecular dynamics simulations to provide structural descriptions of model condensates that mimic nucleolar granular components (GCs). We show that facsimiles of GCs are network fluids featuring spatial inhomogeneities across hierarchies of length scales that reflect the contributions of distinct protein and peptide domains. The network-like inhomogeneous organization is characterized by a coexistence of liquid- and gas-like macromolecular densities that engenders bimodality of internal molecular dynamics. These insights, extracted from a combination of approaches, suggest that condensates formed by multivalent proteins share features with network fluids formed by associative systems such as patchy or hairy colloids.