Sequence and stoichiometry dependence of surface properties of biomolecular condensates

Cells organize many of their internal processes in space and time using condensates formed by liquid-liquid phase separation (LLPS) of biopolymers. Unlike conventional phase separation, biopolymer LLPS typically involves specific, heterotypic interactions between residues or domains, and the stoichiometry and specific sequences of these domains are biologically tunable parameters. Furthermore, LLPS is necessarily accompanied by the emergence of surface tension, which influences the dynamics, permeability, and internal structure of condensates. How does polymer sequence and stoichiometry influence condensate surface structure and surface tension? Using MD simulations, we discovered that the sequence and stoichiometry of heterotypic interaction domains determine the interface entropy, which in turn strongly influences the surface properties of the condensates, suggesting a mechanism of biological regulation.