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Computational models on cell migration

  • Author(s): Shao, Danying
  • et al.
Abstract

Cell migration is one of the most intriguing areas in cell biology and has attracted many interdisciplinary studies. It is regulated by complex biochemical signaling networks and comprises many mechanical processes, including protrusion, adhesion, translocation of the cell body and retraction of the rear. This dissertation starts with the signaling pathway that senses external chemoattractant, specifically, the Ras pathway (Chapter 2). We found that the response of an activated Ras shows near perfect adaptation. We attempted to fit the results using mathematical models for the two possible simple network topologies that can provide perfect adaptation. Only one, the incoherent feedforward network, is able to accurately describe the experimental results. This analysis revealed that adaptation in this Ras pathway is achieved through the proportional activation of upstream components and not through negative feedback loops. From Chapter 3 to Chapter 5, we integrated chemical reactions inside the cell with the mechanical process of cell migration. In Chapter 3, we set up a framework, based on phase field method, to describe the cell shape and the chemical reactions in a moving cell. Under this framework, we developed a computational model on cell morphodynamics in Chapter 4. Our model incorporates the membrane bending force and the surface tension and enforces a constant area. Furthermore, it implements a cross linked actin filament field and an actin bundle field that are responsible for the protrusion and retraction forces, respectively. The model was successfully applied to fish keratocytes and Dictystelium cells. In Chapter 5, we studied the coupling between adhesion mechanism and actin flow in keratocytes. The adhesion mechanism incorporated both the gripping mode and the slipping mode. The model-predicted maps of actin flow, substrate stress and the alignment between the two are quantitatively consistent with experimental observations. Furthermore, we explored the phase diagram of cell migration by varying myosin II and adhesion strength. Our model suggested that the pattern of the actin flow inside the cell, the cell velocity and the cell shape are determined by the integration of actin polymerization, myosin contraction, the adhesion and membrane forces

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