Sequence dependence of biomolecular phase separation

Cells are home to a host of biomolecular condensates – phase-separated droplets that lack a membrane. In addition to nonspecific interactions, phase separation depends on specific binding motifs between constituent molecules. Nevertheless, few rules have been established on how these specific, heterotypic interactions drive phase separation. Using lattice-polymer simulations and mean-field theory, we find that the sequence of binding motifs strongly affects a polymer’s ability to phase separate, influencing both phase boundaries and condensate properties (e.g. viscosity). Notably, sequence primarily acts by determining the conformational entropy of self-bonding by single polymers.