Multivalent polymers can control phase boundary, dynamics, and organization of liquid-liquid phase separation
Name
journal.pone.0245405.pdf
Description
Published version
Size
5.3 MB
Format
Unknown
Checksum (MD5)
8a02afc34659eaf1cd761ea136a88e4a
Author(s)
Zumbro, Emiko
Alexander-Katz, Alfredo
Date Issued
November 2021
Journal
PLoS ONE
Publisher
Public Library of Science (PLoS)
Citation
Zumbro, Emiko and Alexander-Katz, Alfredo. 2021. "Multivalent polymers can control phase boundary, dynamics, and organization of liquid-liquid phase separation." PLoS ONE, 16 (11).
Version
Final published version
Abstract
Multivalent polymers are a key structural component of many biocondensates. When interacting with their cognate binding proteins, multivalent polymers such as RNA and modular proteins have been shown to influence the liquid-liquid phase separation (LLPS) boundary to both control condensate formation and to influence condensate dynamics after phase separation. Much is still unknown about the function and formation of these condensed droplets, but changes in their dynamics or phase separation are associated with neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer’s Disease. Therefore, investigation into how the structure of multivalent polymers relates to changes in biocondensate formation and maturation is essential to understanding and treating these diseases. Here, we use a coarse-grain, Brownian Dynamics simulation with reactive binding that mimics specific interactions in order to investigate the difference between non-specific and specific multivalent binding polymers. We show that non-specific binding interactions can lead to much larger changes in droplet formation at lower protein-polymer interaction energies than their specific, valence-limited counterparts. We also demonstrate the effects of solvent conditions and polymer length on phase separation, and we present how modulating binding energy to the polymer can change the organization of a droplet in a three component system of polymer, binding protein, and solvent. Finally, we compare the effects of surface tension and polymer binding on the condensed phase dynamics, and show that both lower protein solubilities and higher attraction/affinity of the protein to the polymer result in slower droplet dynamics. This research will help to better understand experimental systems and provides additional insight into how multivalent polymers can control LLPS.
MIT Department
Massachusetts Institute of Technology. Department of Materials Science and Engineering
Terms of Use
Creative Commons Attribution 4.0 International License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1371/journal.pone.0245405
