Predicting morphologies of biomolecular condensates from protein interaction networks.

Abstract

The formation of membrane-less organelles in living cells is generally regarded as a result of liquid-liquid phase separation (LLPS). Various condensates can be further assembled into higher-order structures by forming stable interfaces between immiscible phases. For example, stress granules (SGs) form stable interfaces with processing bodies (PBs) under certain conditions, leading to the formation of multiphase condensates. Using a minimal model of a protein interaction network, we demonstrate how a “shared” protein species that partitions into both phases of a multiphase condensate can function as a tunable surfactant that modulates the interfacial properties. In particular, we identify conditions under which a low concentration of this shared species is sufficient to trigger a wetting transition. We also describe a numerical approach that applies classical density functional theory (CDFT) to predict density profiles and surface tensions from the model protein interaction network. Our work shows how low-concentration protein species might function as a biological switch by regulating condensate morphologies.