Localization of protein aggregation in Escherichia coli is governed by diffusion and nucleoid macromolecular crowding effect.

Aggregates of misfolded proteins are a hallmark of many age-related diseases. Recently, they have been linked to aging of Escherichia coli (E. coli) where protein aggregates accumulate at the old pole region of the aging bacterium. Because of the potential of E. coli as a model organism, elucidating...

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Autores principales:	Anne-Sophie Coquel, Jean-Pascal Jacob, Mael Primet, Alice Demarez, Mariella Dimiccoli, Thomas Julou, Lionel Moisan, Ariel B Lindner, Hugues Berry
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/9a44de52057b4aa5be582ff2684e7f3d
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spelling	oai:doaj.org-article:9a44de52057b4aa5be582ff2684e7f3d2021-11-18T05:52:12ZLocalization of protein aggregation in Escherichia coli is governed by diffusion and nucleoid macromolecular crowding effect.1553-734X1553-735810.1371/journal.pcbi.1003038https://doaj.org/article/9a44de52057b4aa5be582ff2684e7f3d2013-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23633942/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Aggregates of misfolded proteins are a hallmark of many age-related diseases. Recently, they have been linked to aging of Escherichia coli (E. coli) where protein aggregates accumulate at the old pole region of the aging bacterium. Because of the potential of E. coli as a model organism, elucidating aging and protein aggregation in this bacterium may pave the way to significant advances in our global understanding of aging. A first obstacle along this path is to decipher the mechanisms by which protein aggregates are targeted to specific intercellular locations. Here, using an integrated approach based on individual-based modeling, time-lapse fluorescence microscopy and automated image analysis, we show that the movement of aging-related protein aggregates in E. coli is purely diffusive (Brownian). Using single-particle tracking of protein aggregates in live E. coli cells, we estimated the average size and diffusion constant of the aggregates. Our results provide evidence that the aggregates passively diffuse within the cell, with diffusion constants that depend on their size in agreement with the Stokes-Einstein law. However, the aggregate displacements along the cell long axis are confined to a region that roughly corresponds to the nucleoid-free space in the cell pole, thus confirming the importance of increased macromolecular crowding in the nucleoids. We thus used 3D individual-based modeling to show that these three ingredients (diffusion, aggregation and diffusion hindrance in the nucleoids) are sufficient and necessary to reproduce the available experimental data on aggregate localization in the cells. Taken together, our results strongly support the hypothesis that the localization of aging-related protein aggregates in the poles of E. coli results from the coupling of passive diffusion-aggregation with spatially non-homogeneous macromolecular crowding. They further support the importance of "soft" intracellular structuring (based on macromolecular crowding) in diffusion-based protein localization in E. coli.Anne-Sophie CoquelJean-Pascal JacobMael PrimetAlice DemarezMariella DimiccoliThomas JulouLionel MoisanAriel B LindnerHugues BerryPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 9, Iss 4, p e1003038 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Anne-Sophie Coquel Jean-Pascal Jacob Mael Primet Alice Demarez Mariella Dimiccoli Thomas Julou Lionel Moisan Ariel B Lindner Hugues Berry Localization of protein aggregation in Escherichia coli is governed by diffusion and nucleoid macromolecular crowding effect.
description	Aggregates of misfolded proteins are a hallmark of many age-related diseases. Recently, they have been linked to aging of Escherichia coli (E. coli) where protein aggregates accumulate at the old pole region of the aging bacterium. Because of the potential of E. coli as a model organism, elucidating aging and protein aggregation in this bacterium may pave the way to significant advances in our global understanding of aging. A first obstacle along this path is to decipher the mechanisms by which protein aggregates are targeted to specific intercellular locations. Here, using an integrated approach based on individual-based modeling, time-lapse fluorescence microscopy and automated image analysis, we show that the movement of aging-related protein aggregates in E. coli is purely diffusive (Brownian). Using single-particle tracking of protein aggregates in live E. coli cells, we estimated the average size and diffusion constant of the aggregates. Our results provide evidence that the aggregates passively diffuse within the cell, with diffusion constants that depend on their size in agreement with the Stokes-Einstein law. However, the aggregate displacements along the cell long axis are confined to a region that roughly corresponds to the nucleoid-free space in the cell pole, thus confirming the importance of increased macromolecular crowding in the nucleoids. We thus used 3D individual-based modeling to show that these three ingredients (diffusion, aggregation and diffusion hindrance in the nucleoids) are sufficient and necessary to reproduce the available experimental data on aggregate localization in the cells. Taken together, our results strongly support the hypothesis that the localization of aging-related protein aggregates in the poles of E. coli results from the coupling of passive diffusion-aggregation with spatially non-homogeneous macromolecular crowding. They further support the importance of "soft" intracellular structuring (based on macromolecular crowding) in diffusion-based protein localization in E. coli.
format	article
author	Anne-Sophie Coquel Jean-Pascal Jacob Mael Primet Alice Demarez Mariella Dimiccoli Thomas Julou Lionel Moisan Ariel B Lindner Hugues Berry
author_facet	Anne-Sophie Coquel Jean-Pascal Jacob Mael Primet Alice Demarez Mariella Dimiccoli Thomas Julou Lionel Moisan Ariel B Lindner Hugues Berry
author_sort	Anne-Sophie Coquel
title	Localization of protein aggregation in Escherichia coli is governed by diffusion and nucleoid macromolecular crowding effect.
title_short	Localization of protein aggregation in Escherichia coli is governed by diffusion and nucleoid macromolecular crowding effect.
title_full	Localization of protein aggregation in Escherichia coli is governed by diffusion and nucleoid macromolecular crowding effect.
title_fullStr	Localization of protein aggregation in Escherichia coli is governed by diffusion and nucleoid macromolecular crowding effect.
title_full_unstemmed	Localization of protein aggregation in Escherichia coli is governed by diffusion and nucleoid macromolecular crowding effect.
title_sort	localization of protein aggregation in escherichia coli is governed by diffusion and nucleoid macromolecular crowding effect.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/9a44de52057b4aa5be582ff2684e7f3d
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Localization of protein aggregation in Escherichia coli is governed by diffusion and nucleoid macromolecular crowding effect.

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