Motif-pattern dependence of biomolecular phase separation driven by specific interactions. Author Benjamin Weiner, Andrew Pyo, Yigal Meir, Ned Wingreen Publication Year 2021 Type Journal Article Abstract Eukaryotic cells partition a wide variety of important materials and processes into biomolecular condensates-phase-separated droplets that lack a membrane. In addition to nonspecific electrostatic or hydrophobic interactions, phase separation also depends on specific binding motifs that link together constituent molecules. Nevertheless, few rules have been established for how these ubiquitous specific, saturating, motif-motif interactions drive phase separation. By integrating Monte Carlo simulations of lattice-polymers with mean-field theory, we show that the sequence of heterotypic 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 single motifs typically form more inter-polymer bonds, which promotes 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. Keywords Animals, Models, Biological, Computational Biology, Protein Binding, Eukaryotic Cells, Entropy, Monte Carlo Method, Biophysical Phenomena, Hydrophobic and Hydrophilic Interactions, Molecular Conformation, Intracellular Space, Viscosity, Polymers Journal PLoS Comput Biol Volume 17 Issue 12 Pages e1009748 Date Published 2021 Dec ISSN Number 1553-7358 DOI 10.1371/journal.pcbi.1009748 Alternate Journal PLoS Comput Biol PMCID PMC8751999 PMID 34965250 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML