Predicting morphology of biomolecular condensates from protein interaction networks

The formation of membraneless organelles in living cells is widely regarded as a result of near-equilibrium phase separation. Various condensates can be further assembled into higher-order structures by forming thermodynamically stable interfaces between immiscible phases. 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. 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 density profiles and surface tensions directly from the model protein 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 condensate morphologies.