Decoding the physical principles of two-component biomolecular phase separation

Cells possess a multiplicity of non-membrane-bound compartments, which form via liquid-liquid phase separation. These condensates assemble and dissolve as needed to enable central cellular functions. One important class of condensates is those composed of two associating polymer species that form on...

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Main Authors: Yaojun Zhang, Bin Xu, Benjamin G Weiner, Yigal Meir, Ned S Wingreen
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2021-03-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/62403
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author Yaojun Zhang
Bin Xu
Benjamin G Weiner
Yigal Meir
Ned S Wingreen
author_facet Yaojun Zhang
Bin Xu
Benjamin G Weiner
Yigal Meir
Ned S Wingreen
author_sort Yaojun Zhang
collection DOAJ
description Cells possess a multiplicity of non-membrane-bound compartments, which form via liquid-liquid phase separation. These condensates assemble and dissolve as needed to enable central cellular functions. One important class of condensates is those composed of two associating polymer species that form one-to-one specific bonds. What are the physical principles that underlie phase separation in such systems? To address this question, we employed coarse-grained molecular dynamics simulations to examine how the phase boundaries depend on polymer valence, stoichiometry, and binding strength. We discovered a striking phenomenon – for sufficiently strong binding, phase separation is suppressed at rational polymer stoichiometries, which we termed the magic-ratio effect. We further developed an analytical dimer-gel theory that confirmed the magic-ratio effect and disentangled the individual roles of polymer properties in shaping the phase diagram. Our work provides new insights into the factors controlling the phase diagrams of biomolecular condensates, with implications for natural and synthetic systems.
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spelling doaj.art-d81782be91ee4778ae794ec7182414e02022-12-22T04:32:49ZengeLife Sciences Publications LtdeLife2050-084X2021-03-011010.7554/eLife.62403Decoding the physical principles of two-component biomolecular phase separationYaojun Zhang0https://orcid.org/0000-0003-4587-6834Bin Xu1Benjamin G Weiner2https://orcid.org/0000-0002-1995-8660Yigal Meir3Ned S Wingreen4https://orcid.org/0000-0001-7384-2821Center for the Physics of Biological Function, Princeton University, Princeton, United StatesDepartment of Physics, Princeton University, Princeton, United StatesDepartment of Physics, Princeton University, Princeton, United StatesDepartment of Physics, Princeton University, Princeton, United States; Department of Physics, Ben Gurion University of the Negev, Beersheba, Israel; Department of Molecular Biology, Princeton University, Princeton, United StatesDepartment of Molecular Biology, Princeton University, Princeton, United States; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United StatesCells possess a multiplicity of non-membrane-bound compartments, which form via liquid-liquid phase separation. These condensates assemble and dissolve as needed to enable central cellular functions. One important class of condensates is those composed of two associating polymer species that form one-to-one specific bonds. What are the physical principles that underlie phase separation in such systems? To address this question, we employed coarse-grained molecular dynamics simulations to examine how the phase boundaries depend on polymer valence, stoichiometry, and binding strength. We discovered a striking phenomenon – for sufficiently strong binding, phase separation is suppressed at rational polymer stoichiometries, which we termed the magic-ratio effect. We further developed an analytical dimer-gel theory that confirmed the magic-ratio effect and disentangled the individual roles of polymer properties in shaping the phase diagram. Our work provides new insights into the factors controlling the phase diagrams of biomolecular condensates, with implications for natural and synthetic systems.https://elifesciences.org/articles/62403phase separationbiomolecular condensatesassociative polymersmolecular dynamics simulations
spellingShingle Yaojun Zhang
Bin Xu
Benjamin G Weiner
Yigal Meir
Ned S Wingreen
Decoding the physical principles of two-component biomolecular phase separation
eLife
phase separation
biomolecular condensates
associative polymers
molecular dynamics simulations
title Decoding the physical principles of two-component biomolecular phase separation
title_full Decoding the physical principles of two-component biomolecular phase separation
title_fullStr Decoding the physical principles of two-component biomolecular phase separation
title_full_unstemmed Decoding the physical principles of two-component biomolecular phase separation
title_short Decoding the physical principles of two-component biomolecular phase separation
title_sort decoding the physical principles of two component biomolecular phase separation
topic phase separation
biomolecular condensates
associative polymers
molecular dynamics simulations
url https://elifesciences.org/articles/62403
work_keys_str_mv AT yaojunzhang decodingthephysicalprinciplesoftwocomponentbiomolecularphaseseparation
AT binxu decodingthephysicalprinciplesoftwocomponentbiomolecularphaseseparation
AT benjamingweiner decodingthephysicalprinciplesoftwocomponentbiomolecularphaseseparation
AT yigalmeir decodingthephysicalprinciplesoftwocomponentbiomolecularphaseseparation
AT nedswingreen decodingthephysicalprinciplesoftwocomponentbiomolecularphaseseparation