Decoding the physical principles of two-component biomolecular phase separation.

TitleDecoding the physical principles of two-component biomolecular phase separation.
Publication TypeJournal Article
Year of Publication2021
AuthorsZhang, Y, Xu, B, Weiner, BG, Meir, Y, Wingreen, NS
JournalElife
Volume10
Date Published2021 Mar 11
ISSN2050-084X
Abstract

<p>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.</p>

DOI10.7554/eLife.62403
Alternate JournalElife
PubMed ID33704061
PubMed Central IDPMC7952089
Grant ListPHY 1734030 / / National Science Foundation /
PHY 1521553 / / National Science Foundation /