Sequence dependence of biomolecular phase separation

Benjamin G Weiner, Yigal Meir, Ned S Wingreen

Research output: Working paper/PreprintPreprint


Cells are home to a wide variety 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 show 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 and polymer diffusion). We find that sequences with large blocks of a single motif typically form more inter-polymer bonds which promote phase separation. Notably, the sequence of binding motifs influences phase separation primarily by determining the conformational entropy of self-bonding by single polymers. This contrasts with systems where the molecular architecture primarily affects the energy of the dense phase, providing a new entropy-based mechanism for the biological control of phase separation.
Original languageEnglish GB
StatePublished - 2021

Publication series

PublisherCold Spring Harbor Laboratory Press


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