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About the Authors:
Jian-Geng Chiou
Roles Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Software, Visualization, Writing - original draft, Writing - review & editing
Affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, United States of America
ORCID http://orcid.org/0000-0003-3246-5841
Samuel A. Ramirez
Roles Formal analysis, Validation, Writing - review & editing
Affiliation: Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
Timothy C. Elston
Roles Formal analysis, Validation, Writing - review & editing
Affiliation: Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
ORCID http://orcid.org/0000-0002-4601-2117
Thomas P. Witelski
Roles Formal analysis, Methodology, Validation, Writing - review & editing
Affiliation: Department of Mathematics, Duke University, Durham, North Carolina, United States of America
ORCID http://orcid.org/0000-0003-0789-9859
David G. Schaeffer
Roles Formal analysis, Validation, Writing - review & editing
Affiliation: Department of Mathematics, Duke University, Durham, North Carolina, United States of America
Daniel J. Lew
Roles Conceptualization, Funding acquisition, Resources, Supervision, Writing - review & editing
* E-mail: [email protected]
Affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, United States of AmericaAbstract
Rho-GTPases are master regulators of polarity establishment and cell morphology. Positive feedback enables concentration of Rho-GTPases into clusters at the cell cortex, from where they regulate the cytoskeleton. Different cell types reproducibly generate either one (e.g. the front of a migrating cell) or several clusters (e.g. the multiple dendrites of a neuron), but the mechanistic basis for unipolar or multipolar outcomes is unclear. The design principles of Rho-GTPase circuits are captured by two-component reaction-diffusion models based on conserved aspects of Rho-GTPase biochemistry. Some such models display rapid winner-takes-all competition between clusters, yielding a unipolar outcome. Other models allow prolonged co-existence of clusters. We investigate the behavior of a simple class of models and show that while the timescale of competition varies enormously depending on model parameters, a single factor explains a large majority of this variation. The dominant factor concerns the degree to which the maximal active GTPase concentration in a cluster approaches a “saturation point” determined by model parameters. We suggest that both saturation and the effect of saturation on competition reflect fundamental properties of the...