Predicting the Morphology of Multiphase Biomolecular Condensates from Protein Interaction Networks

Phase-separated biomolecular condensates containing proteins and RNAs can assemble into higher-order structures by forming thermodynamically stable interfaces between immiscible phases. Using a minimal model of a protein/RNA 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. We use Monte Carlo simulations and free-energy calculations to identify conditions under which a low concentration of this shared species is sufficient to trigger a wetting transition. We also describe a numerical approach based on classical density functional theory to predict concentration profiles and surface tensions directly from the model protein/RNA interaction network. Finally, we show that the wetting phase diagrams that emerge from our calculations can be understood in terms of a simple model of selective adsorption to a fluctuating interface. Our work shows how a low-concentration protein species might function as a biological switch for regulating multiphase condensate morphologies.