A novel stochastic simulation approach enables exploration of mechanisms for regulating polarity site movement.

Cells polarize their movement or growth toward external directional cues in many different contexts. For example, budding yeast cells grow toward potential mating partners in response to pheromone gradients. Directed growth is controlled by polarity factors that assemble into clusters at the cell me...

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Autores principales:	Samuel A Ramirez, Michael Pablo, Sean Burk, Daniel J Lew, Timothy C Elston
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/838e930338424d3a95882d04a4663ebc
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id	oai:doaj.org-article:838e930338424d3a95882d04a4663ebc
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spelling	oai:doaj.org-article:838e930338424d3a95882d04a4663ebc2021-12-02T19:57:32ZA novel stochastic simulation approach enables exploration of mechanisms for regulating polarity site movement.1553-734X1553-735810.1371/journal.pcbi.1008525https://doaj.org/article/838e930338424d3a95882d04a4663ebc2021-07-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1008525https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Cells polarize their movement or growth toward external directional cues in many different contexts. For example, budding yeast cells grow toward potential mating partners in response to pheromone gradients. Directed growth is controlled by polarity factors that assemble into clusters at the cell membrane. The clusters assemble, disassemble, and move between different regions of the membrane before eventually forming a stable polarity site directed toward the pheromone source. Pathways that regulate clustering have been identified but the molecular mechanisms that regulate cluster mobility are not well understood. To gain insight into the contribution of chemical noise to cluster behavior we simulated clustering using the reaction-diffusion master equation (RDME) framework to account for molecular-level fluctuations. RDME simulations are a computationally efficient approximation, but their results can diverge from the underlying microscopic dynamics. We implemented novel concentration-dependent rate constants that improved the accuracy of RDME-based simulations, allowing us to efficiently investigate how cluster dynamics might be regulated. Molecular noise was effective in relocating clusters when the clusters contained low numbers of limiting polarity factors, and when Cdc42, the central polarity regulator, exhibited short dwell times at the polarity site. Cluster stabilization occurred when abundances or binding rates were altered to either lengthen dwell times or increase the number of polarity molecules in the cluster. We validated key results using full 3D particle-based simulations. Understanding the mechanisms cells use to regulate the dynamics of polarity clusters should provide insights into how cells dynamically track external directional cues.Samuel A RamirezMichael PabloSean BurkDaniel J LewTimothy C ElstonPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 7, p e1008525 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Samuel A Ramirez Michael Pablo Sean Burk Daniel J Lew Timothy C Elston A novel stochastic simulation approach enables exploration of mechanisms for regulating polarity site movement.
description	Cells polarize their movement or growth toward external directional cues in many different contexts. For example, budding yeast cells grow toward potential mating partners in response to pheromone gradients. Directed growth is controlled by polarity factors that assemble into clusters at the cell membrane. The clusters assemble, disassemble, and move between different regions of the membrane before eventually forming a stable polarity site directed toward the pheromone source. Pathways that regulate clustering have been identified but the molecular mechanisms that regulate cluster mobility are not well understood. To gain insight into the contribution of chemical noise to cluster behavior we simulated clustering using the reaction-diffusion master equation (RDME) framework to account for molecular-level fluctuations. RDME simulations are a computationally efficient approximation, but their results can diverge from the underlying microscopic dynamics. We implemented novel concentration-dependent rate constants that improved the accuracy of RDME-based simulations, allowing us to efficiently investigate how cluster dynamics might be regulated. Molecular noise was effective in relocating clusters when the clusters contained low numbers of limiting polarity factors, and when Cdc42, the central polarity regulator, exhibited short dwell times at the polarity site. Cluster stabilization occurred when abundances or binding rates were altered to either lengthen dwell times or increase the number of polarity molecules in the cluster. We validated key results using full 3D particle-based simulations. Understanding the mechanisms cells use to regulate the dynamics of polarity clusters should provide insights into how cells dynamically track external directional cues.
format	article
author	Samuel A Ramirez Michael Pablo Sean Burk Daniel J Lew Timothy C Elston
author_facet	Samuel A Ramirez Michael Pablo Sean Burk Daniel J Lew Timothy C Elston
author_sort	Samuel A Ramirez
title	A novel stochastic simulation approach enables exploration of mechanisms for regulating polarity site movement.
title_short	A novel stochastic simulation approach enables exploration of mechanisms for regulating polarity site movement.
title_full	A novel stochastic simulation approach enables exploration of mechanisms for regulating polarity site movement.
title_fullStr	A novel stochastic simulation approach enables exploration of mechanisms for regulating polarity site movement.
title_full_unstemmed	A novel stochastic simulation approach enables exploration of mechanisms for regulating polarity site movement.
title_sort	novel stochastic simulation approach enables exploration of mechanisms for regulating polarity site movement.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/838e930338424d3a95882d04a4663ebc
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_version_	1718375849647931392

A novel stochastic simulation approach enables exploration of mechanisms for regulating polarity site movement.

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