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A Mechanochemical Model for Neutrophil Polarization

Kopfer, Kai Harold

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Abstract

Directed migration of eukaryotic cells is caused by a polarization of the actomyosin cytoskeleton (ACM). Throughout many cell types the polar alignment of the AMC is i.a. initiated by the activation of the Rho GTPases Rac and RhoA. In response to an external chemical gradient active Rac accumulates and determines the cell front, while active RhoA predominantly accumulates at the rear of the cell. Current experimental evidence indicates that in neutrophils mechanical tension of the plasma membrane confines Rac activity patterns to the leading front. The patterning mechanism behind the Rho-based polarization process of eukaryotic cells has interested mathematical modellers over the last decades. While elaborated concepts for purely biochemical and purely mechanical patterning processes are available, the basics of mechanochemical patterning with respect to cell polarization are not well understood yet. In accordance to the aforementioned experimental findings, a mechanochemical model for cell polarization is suggested, including Rho GTPase mediated AMC dynamics and changes in membrane tension as upstream controller of Rho GTP, in which active Rac patterns are locally confined to the cell front by membrane ten- sion. Rho proteins can become activated or inactivated due to complex formation with specific effector proteins. In the model active Rac and active RhoA mediate actin polymerization and the generation of myosin-dependent contractile force, respectively. The model cell is considered as a two dimensional layer adhering to a flat substrate, wherein the embedded AMC is modelled as a viscous active gel. Morphological changes of the AMC induce changes in membrane tension. Rho based chemical signalling is modelled by reaction-diffusion equations. Chemical signalling induces a mechanical response of the AMC. Actomyosin mechanics are modelled by a Stokes-related equation. The spatial change of the domain is determined by a free-boundary problem. The model accounts for a minimal mechanochemical circuit capable of generating robust polarity patterns and demonstrates how cell mechanics could serve as a long range signal transmitter in Rho based cell polarization.

Item Type: Dissertation
Supervisor: Jäger, Prof. Dr. Dr. h.c. mult. Willi
Date of thesis defense: 24 May 2018
Date Deposited: 03 Dec 2018 10:26
Date: 2018
Faculties / Institutes: The Faculty of Mathematics and Computer Science > Department of Applied Mathematics
Subjects: 510 Mathematics
570 Life sciences
Controlled Keywords: Musterbildung, Dynamische Modellierung, Geometrische Modellierung, Zellmigration, Chemotaxis
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