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Multivalent polymers can control phase boundary, dynamics, and organization of liquid-liquid phase separation

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...

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Detalles Bibliográficos
Autores principales: Zumbro, Emiko, Alexander-Katz, Alfredo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8575181/
https://www.ncbi.nlm.nih.gov/pubmed/34748548
http://dx.doi.org/10.1371/journal.pone.0245405
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author Zumbro, Emiko
Alexander-Katz, Alfredo
author_facet Zumbro, Emiko
Alexander-Katz, Alfredo
author_sort Zumbro, Emiko
collection PubMed
description 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.
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spelling pubmed-85751812021-11-09 Multivalent polymers can control phase boundary, dynamics, and organization of liquid-liquid phase separation Zumbro, Emiko Alexander-Katz, Alfredo PLoS One Research Article 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. Public Library of Science 2021-11-08 /pmc/articles/PMC8575181/ /pubmed/34748548 http://dx.doi.org/10.1371/journal.pone.0245405 Text en © 2021 Zumbro, Alexander-Katz https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Zumbro, Emiko
Alexander-Katz, Alfredo
Multivalent polymers can control phase boundary, dynamics, and organization of liquid-liquid phase separation
title Multivalent polymers can control phase boundary, dynamics, and organization of liquid-liquid phase separation
title_full Multivalent polymers can control phase boundary, dynamics, and organization of liquid-liquid phase separation
title_fullStr Multivalent polymers can control phase boundary, dynamics, and organization of liquid-liquid phase separation
title_full_unstemmed Multivalent polymers can control phase boundary, dynamics, and organization of liquid-liquid phase separation
title_short Multivalent polymers can control phase boundary, dynamics, and organization of liquid-liquid phase separation
title_sort multivalent polymers can control phase boundary, dynamics, and organization of liquid-liquid phase separation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8575181/
https://www.ncbi.nlm.nih.gov/pubmed/34748548
http://dx.doi.org/10.1371/journal.pone.0245405
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