Motif-pattern dependence of biomolecular phase separation driven by specific interactions

Benjamin G. Weiner; Andrew G.T. Pyo; Yigal Meir; Ned S. Wingreen

doi:10.1371/journal.pcbi.1009748

Motif-pattern dependence of biomolecular phase separation driven by specific interactions

Benjamin G. Weiner, Andrew G.T. Pyo, Yigal Meir, Ned S. Wingreen

Princeton University

Research output: Contribution to journal › Article › peer-review

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.

Original language	American English
Article number	e1009748
Journal	PLoS computational biology
Volume	17
Issue number	12
DOIs	https://doi.org/10.1371/journal.pcbi.1009748
State	Published - Dec 2021

ASJC Scopus subject areas

Ecology, Evolution, Behavior and Systematics
Modeling and Simulation
Ecology
Molecular Biology
Genetics
Cellular and Molecular Neuroscience
Computational Theory and Mathematics

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10.1371/journal.pcbi.1009748

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title = "Motif-pattern dependence of biomolecular phase separation driven by specific interactions",

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{\textquoteright}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.",

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N1 - Publisher Copyright: Copyright: © 2021 Weiner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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N2 - 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.

AB - 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.

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Motif-pattern dependence of biomolecular phase separation driven by specific interactions

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