Spatial Stochastic Dynamics Enable Robust Cell Polarization
Abstract
Although cell polarity is an essential feature of living cells, it is far from being well-understood. Using a combination of computational modeling and biological experiments we closely examine an important prototype of cell polarity: the pheromone-induced formation of the yeast polarisome. Focusing on the role of noise and spatial heterogeneity, we develop and investigate two mechanistic spatial models of polarisome formation, one deterministic and the other stochastic, and compare the contrasting predictions of these two models against experimental phenotypes of wild-type and mutant cells. We find that the stochastic model can more robustly reproduce two fundamental characteristics observed in wild-type cells: a highly polarized phenotype via a mechanism that we refer to as spatial stochastic amplification, and the ability of the polarisome to track a moving pheromone input. Moreover, we find that only the stochastic model can simultaneously reproduce these characteristics of the wild-type phenotype and the multi-polarisome phenotype of a deletion mutant of the scaffolding protein Spa2. Significantly, our analysis also demonstrates that higher levels of stochastic noise results in increased robustness of polarization to parameter variation. Furthermore, our work suggests a novel role for a polarisome protein in the stabilization of actin cables. These findings elucidate the intricatemore »
- Authors:
-
- University of California, Santa Barbara, CA (United States)
- University of California, Santa Barbara, CA (United States); Eidgenoessische Technische Hochschule (ETH), Zurich (Switzerland)
- Publication Date:
- Research Org.:
- Univ. of California, Santa Barbara, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC); National Science Foundation (NSF); US Army Research Office (ARO); National Institutes of Health (NIH)
- OSTI Identifier:
- 1904675
- Grant/Contract Number:
- FG02-04ER25621; DMS-1001012, DMS-1001006, IGERT DGE-02-21715; ECCS-0835847; W911NF-09-0001; R01-EB014877-01
- Resource Type:
- Accepted Manuscript
- Journal Name:
- PLoS Computational Biology (Online)
- Additional Journal Information:
- Journal Name: PLoS Computational Biology (Online); Journal Volume: 9; Journal Issue: 7; Journal ID: ISSN 1553-7358
- Publisher:
- Public Library of Science
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; cell polarity; actins; biochemical simulations; signal amplification; yeast; depolymerization; yeast and fungal models; actin polymerization
Citation Formats
Lawson, Michael J., Drawert, Brian, Khammash, Mustafa, Petzold, Linda, and Yi, Tau-Mu. Spatial Stochastic Dynamics Enable Robust Cell Polarization. United States: N. p., 2013.
Web. doi:10.1371/journal.pcbi.1003139.
Lawson, Michael J., Drawert, Brian, Khammash, Mustafa, Petzold, Linda, & Yi, Tau-Mu. Spatial Stochastic Dynamics Enable Robust Cell Polarization. United States. https://doi.org/10.1371/journal.pcbi.1003139
Lawson, Michael J., Drawert, Brian, Khammash, Mustafa, Petzold, Linda, and Yi, Tau-Mu. Thu .
"Spatial Stochastic Dynamics Enable Robust Cell Polarization". United States. https://doi.org/10.1371/journal.pcbi.1003139. https://www.osti.gov/servlets/purl/1904675.
@article{osti_1904675,
title = {Spatial Stochastic Dynamics Enable Robust Cell Polarization},
author = {Lawson, Michael J. and Drawert, Brian and Khammash, Mustafa and Petzold, Linda and Yi, Tau-Mu},
abstractNote = {Although cell polarity is an essential feature of living cells, it is far from being well-understood. Using a combination of computational modeling and biological experiments we closely examine an important prototype of cell polarity: the pheromone-induced formation of the yeast polarisome. Focusing on the role of noise and spatial heterogeneity, we develop and investigate two mechanistic spatial models of polarisome formation, one deterministic and the other stochastic, and compare the contrasting predictions of these two models against experimental phenotypes of wild-type and mutant cells. We find that the stochastic model can more robustly reproduce two fundamental characteristics observed in wild-type cells: a highly polarized phenotype via a mechanism that we refer to as spatial stochastic amplification, and the ability of the polarisome to track a moving pheromone input. Moreover, we find that only the stochastic model can simultaneously reproduce these characteristics of the wild-type phenotype and the multi-polarisome phenotype of a deletion mutant of the scaffolding protein Spa2. Significantly, our analysis also demonstrates that higher levels of stochastic noise results in increased robustness of polarization to parameter variation. Furthermore, our work suggests a novel role for a polarisome protein in the stabilization of actin cables. These findings elucidate the intricate role of spatial stochastic effects in cell polarity, giving support to a cellular model where noise and spatial heterogeneity combine to achieve robust biological function.},
doi = {10.1371/journal.pcbi.1003139},
journal = {PLoS Computational Biology (Online)},
number = 7,
volume = 9,
place = {United States},
year = {Thu Jul 25 00:00:00 EDT 2013},
month = {Thu Jul 25 00:00:00 EDT 2013}
}
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