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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Autores principales:	Emiko Zumbro, Alfredo Alexander-Katz
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a353a3aa0c4d469bac23100b842aa10d
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spelling	oai:doaj.org-article:a353a3aa0c4d469bac23100b842aa10d2021-11-18T06:34:28ZMultivalent polymers can control phase boundary, dynamics, and organization of liquid-liquid phase separation1932-6203https://doaj.org/article/a353a3aa0c4d469bac23100b842aa10d2021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8575181/?tool=EBIhttps://doaj.org/toc/1932-6203Multivalent 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.Emiko ZumbroAlfredo Alexander-KatzPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Emiko Zumbro Alfredo Alexander-Katz Multivalent polymers can control phase boundary, dynamics, and organization of liquid-liquid phase separation
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.
format	article
author	Emiko Zumbro Alfredo Alexander-Katz
author_facet	Emiko Zumbro Alfredo Alexander-Katz
author_sort	Emiko Zumbro
title	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_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_sort	multivalent polymers can control phase boundary, dynamics, and organization of liquid-liquid phase separation
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/a353a3aa0c4d469bac23100b842aa10d
work_keys_str_mv	AT emikozumbro multivalentpolymerscancontrolphaseboundarydynamicsandorganizationofliquidliquidphaseseparation AT alfredoalexanderkatz multivalentpolymerscancontrolphaseboundarydynamicsandorganizationofliquidliquidphaseseparation
_version_	1718424497549213696

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

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