Liquid network connectivity regulates the stability and composition of biomolecular condensates with many components

TLDR

Liquid–liquid phase separation drives the spatial organization of diverse cellular molecules by forming biomolecular condensates. The study seeks to derive predictive rules for the stability and composition of multicomponent biomolecular condensates. The authors employ simulations to establish these predictive rules. Simulations show that biomolecules enhancing condensate connectivity are enriched, connectivity raises critical temperatures, and thus the composition of highly multicomponent condensates can be predicted from the critical points of reduced-component mixtures, extending the link between phase behavior and critical parameters such as temperature, pH, and salt concentration.

Abstract

Significance LLPS plays an important role in the spatiotemporal organization of the numerous molecular constituents of living cells, via formation of biomolecular condensates. Our simulations provide predictive rules governing the stability and composition of multicomponent biomolecular condensates. Biomolecules that increase the molecular connectivity of condensates are present in higher concentrations because connectivity is positively correlated with stability. Greater connectivity within highly multicomponent condensates manifests in higher critical temperatures in the phase diagrams of accessible systems involving just a few components. Hence, composition of highly multicomponent condensates can be predicted from the critical points of reduced-component mixtures. Our findings expand the mechanisms relating phase behavior of multicomponent intracellular mixtures to critical parameters (temperature, pH, salt concentration, etc.) of the constituent biomolecules.