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

Liquid-liquid phase separation plays an important role in the spatiotemporal organization of the numerous molecular constituents of living cells, via formation of biomolecular condensates¹. Using a minimal coarse-grained model that allows us to simulate thousands of interacting multivalent proteins, we 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 findings² expand the mechanisms relating phase behavior of multicomponent intracellular mixtures to critical parameters (temperature, pH, salt concentration, etc.) of the constituent biomolecules.

References:
1) Brangwynne et al. Science 324, 1729-1732 (2009).
2) Espinosa et al. Proc. Nat. Acad. Sci. U.S.A. 117, 13238-13247 (2020).