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Colloid osmotic parameterization and measurement of subcellular crowding

Crowding of the subcellular environment by macromolecules is thought to promote protein aggregation and phase separation. A challenge is how to parameterize the degree of crowding of the cell interior or artificial solutions that is relevant to these reactions. Here I review colloid osmotic pressure...

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Autor principal: Mitchison, T. J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589563/
https://www.ncbi.nlm.nih.gov/pubmed/30640588
http://dx.doi.org/10.1091/mbc.E18-09-0549
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author Mitchison, T. J.
author_facet Mitchison, T. J.
author_sort Mitchison, T. J.
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description Crowding of the subcellular environment by macromolecules is thought to promote protein aggregation and phase separation. A challenge is how to parameterize the degree of crowding of the cell interior or artificial solutions that is relevant to these reactions. Here I review colloid osmotic pressure as a crowding metric. This pressure is generated by solutions of macromolecules in contact with pores that are permeable to water and ions but not macromolecules. It generates depletion forces that push macromolecules together in crowded solutions and thus promotes aggregation and phase separation. I discuss measurements of colloid osmotic pressure inside cells using the nucleus, the cytoplasmic gel, and fluorescence resonant energy transfer (FRET) biosensors as osmometers, which return a range of values from 1 to 20 kPa. I argue for a low value, 1–2 kPa, in frog eggs and perhaps more generally. This value is close to the linear range on concentration–pressure curves and is thus not crowded from an osmotic perspective. I discuss the implications of a low crowding pressure inside cells for phase separation biology, buffer design, and proteome evolution. I also discuss a pressure–tension model for nuclear shape, where colloid osmotic pressure generated by nuclear protein import inflates the nucleus.
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spelling pubmed-65895632019-06-28 Colloid osmotic parameterization and measurement of subcellular crowding Mitchison, T. J. Mol Biol Cell Perspectives Crowding of the subcellular environment by macromolecules is thought to promote protein aggregation and phase separation. A challenge is how to parameterize the degree of crowding of the cell interior or artificial solutions that is relevant to these reactions. Here I review colloid osmotic pressure as a crowding metric. This pressure is generated by solutions of macromolecules in contact with pores that are permeable to water and ions but not macromolecules. It generates depletion forces that push macromolecules together in crowded solutions and thus promotes aggregation and phase separation. I discuss measurements of colloid osmotic pressure inside cells using the nucleus, the cytoplasmic gel, and fluorescence resonant energy transfer (FRET) biosensors as osmometers, which return a range of values from 1 to 20 kPa. I argue for a low value, 1–2 kPa, in frog eggs and perhaps more generally. This value is close to the linear range on concentration–pressure curves and is thus not crowded from an osmotic perspective. I discuss the implications of a low crowding pressure inside cells for phase separation biology, buffer design, and proteome evolution. I also discuss a pressure–tension model for nuclear shape, where colloid osmotic pressure generated by nuclear protein import inflates the nucleus. The American Society for Cell Biology 2019-01-15 /pmc/articles/PMC6589563/ /pubmed/30640588 http://dx.doi.org/10.1091/mbc.E18-09-0549 Text en © 2019 Mitchison. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.
spellingShingle Perspectives
Mitchison, T. J.
Colloid osmotic parameterization and measurement of subcellular crowding
title Colloid osmotic parameterization and measurement of subcellular crowding
title_full Colloid osmotic parameterization and measurement of subcellular crowding
title_fullStr Colloid osmotic parameterization and measurement of subcellular crowding
title_full_unstemmed Colloid osmotic parameterization and measurement of subcellular crowding
title_short Colloid osmotic parameterization and measurement of subcellular crowding
title_sort colloid osmotic parameterization and measurement of subcellular crowding
topic Perspectives
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589563/
https://www.ncbi.nlm.nih.gov/pubmed/30640588
http://dx.doi.org/10.1091/mbc.E18-09-0549
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