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Macromolecular crowding directs the motion of small molecules inside cells

It is now well established that cell interiors are significantly crowded by macromolecules, which impede diffusion and enhance binding rates. However, it is not fully appreciated that levels of crowding are heterogeneous, and can vary substantially between subcellular regions. In this article, start...

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Detalles Bibliográficos
Autores principales: Smith, Stephen, Cianci, Claudia, Grima, Ramon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493789/
https://www.ncbi.nlm.nih.gov/pubmed/28615492
http://dx.doi.org/10.1098/rsif.2017.0047
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author Smith, Stephen
Cianci, Claudia
Grima, Ramon
author_facet Smith, Stephen
Cianci, Claudia
Grima, Ramon
author_sort Smith, Stephen
collection PubMed
description It is now well established that cell interiors are significantly crowded by macromolecules, which impede diffusion and enhance binding rates. However, it is not fully appreciated that levels of crowding are heterogeneous, and can vary substantially between subcellular regions. In this article, starting from a microscopic model, we derive coupled nonlinear partial differential equations for the concentrations of two populations of large and small spherical particles with steric volume exclusion. By performing an expansion in the ratio of the particle sizes, we find that the diffusion of a small particle in the presence of large particles obeys an advection–diffusion equation, with a reduced diffusion coefficient and a velocity directed towards less crowded regions. The interplay between advection and diffusion leads to behaviour that differs significantly from Brownian diffusion. We show that biologically plausible distributions of macromolecules can lead to highly non-Gaussian probability densities for the small particle position, including asymmetrical and multimodal densities. We confirm all our results using hard-sphere Brownian dynamics simulations.
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spelling pubmed-54937892017-07-09 Macromolecular crowding directs the motion of small molecules inside cells Smith, Stephen Cianci, Claudia Grima, Ramon J R Soc Interface Life Sciences–Mathematics interface It is now well established that cell interiors are significantly crowded by macromolecules, which impede diffusion and enhance binding rates. However, it is not fully appreciated that levels of crowding are heterogeneous, and can vary substantially between subcellular regions. In this article, starting from a microscopic model, we derive coupled nonlinear partial differential equations for the concentrations of two populations of large and small spherical particles with steric volume exclusion. By performing an expansion in the ratio of the particle sizes, we find that the diffusion of a small particle in the presence of large particles obeys an advection–diffusion equation, with a reduced diffusion coefficient and a velocity directed towards less crowded regions. The interplay between advection and diffusion leads to behaviour that differs significantly from Brownian diffusion. We show that biologically plausible distributions of macromolecules can lead to highly non-Gaussian probability densities for the small particle position, including asymmetrical and multimodal densities. We confirm all our results using hard-sphere Brownian dynamics simulations. The Royal Society 2017-06 2017-06-14 /pmc/articles/PMC5493789/ /pubmed/28615492 http://dx.doi.org/10.1098/rsif.2017.0047 Text en © 2017 The Author(s). http://creativecommons.org/licenses/by/4.0/ Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
spellingShingle Life Sciences–Mathematics interface
Smith, Stephen
Cianci, Claudia
Grima, Ramon
Macromolecular crowding directs the motion of small molecules inside cells
title Macromolecular crowding directs the motion of small molecules inside cells
title_full Macromolecular crowding directs the motion of small molecules inside cells
title_fullStr Macromolecular crowding directs the motion of small molecules inside cells
title_full_unstemmed Macromolecular crowding directs the motion of small molecules inside cells
title_short Macromolecular crowding directs the motion of small molecules inside cells
title_sort macromolecular crowding directs the motion of small molecules inside cells
topic Life Sciences–Mathematics interface
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493789/
https://www.ncbi.nlm.nih.gov/pubmed/28615492
http://dx.doi.org/10.1098/rsif.2017.0047
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