Anomalous Long-range Hard-wall Repulsion between Polymers in Solvent Mixtures and Its Implication for Biomolecular Condensates

Abstract: The system of polymers in solvent mixtures is a widely-used model to represent biomolecular condensates in intracellular environments. Here, we apply a variational theory to control the center-of-mass of two polymers and perform the first quantification of their interactions in solvent mixtures. Even both solvent and cosolvent are good to the polymer, we demonstrate that strong polymer-cosolvent affinity induces the formation of a single-chain condensate. Even though all the molecular interactions are soft, the potential of mean force between two condensates exhibits an anomalous feature of long-range hard-wall repulsion, which cannot be categorized into any existing types of inter-chain interactions. This repulsion is enhanced as either the affinity or the bulk cosolvent fraction increases. The underlying mechanism is cosolvent regulation manifested as a discontinuous local condensation of cosolvent. The hard-wall repulsion provides a kinetic barrier to prevent coalescence of condensates and hence highlights the intrinsic role of proteins as a cosolvent in stabilizing biomolecular condensates.