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

TL;DR

This study reveals a novel long-range hard-wall repulsion between polymers in solvent mixtures, which influences biomolecular condensate stability and is driven by cosolvent regulation and local condensation effects.

Contribution

First quantification of polymer interactions in solvent mixtures showing anomalous long-range repulsion, highlighting the role of cosolvent in condensate stabilization.

Findings

Long-range hard-wall repulsion observed between polymers.

Increased affinity or cosolvent fraction enhances repulsion.

Cosolvent regulation causes local condensation and kinetic barriers.

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.