4.4 Article

A computational model of cell migration coupling the growth of focal adhesions with oscillatory cell protrusions

Journal

JOURNAL OF THEORETICAL BIOLOGY
Volume 253, Issue 4, Pages 701-716

Publisher

ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jtbi.2008.04.035

Keywords

motility; actin dynamics; focal adhesion; random migration; integrative modeling

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Cell migration is a highly integrated process where actin turnover, actomyosin contractility, and adhesion dynamics are all closely linked. In this paper, we propose a computational model investigating the coupling of these fundamental processes within the context of spontaneous (i.e. unstimulated) cell migration. In the unstimulated cell, membrane oscillations originating from the interaction between passive hydrostatic pressure and contractility are sufficient to lead to the formation of adhesion spots. Cell contractility then leads to the maturation of these adhesion spots into focal adhesions. Due to active actin polymerization, which reinforces protrusion at the leading edge, the traction force required for cell translocation can be generated. Computational simulations first show that the model hypotheses allow one to reproduce the main features of fibroblast cell migration and established results on the biphasic aspect of the cell speed as a function of adhesion strength. The model also demonstrates that certain temporal parameters, such as the adhesion proteins recycling time and adhesion lifetimes, influence cell motion patterns, particularly cell speed and persistence of the direction of migration. This study provides some elements, which allow a better understanding of spontaneous cell migration and enables a first glance at how an individual cell would potentially react once exposed to a stimulus. (C) 2008 Elsevier Ltd. All rights reserved.

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