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Annals of Biomedical Engineering

, Volume 27, Issue 2, pp 219–235 | Cite as

Kinetic Model for Integrin-mediated Adhesion Release During Cell Migration

  • Sean P. Palecek
  • Alan F. Horwitz
  • Douglas A. Lauffenburger
Article

Abstract

Under many circumstances, cell migration speed is limited by the rate of cell-substratum detachment at the cell rear. We have constructed a mathematical model to integrate how the biophysical and biochemical interactions between integrins, the cytoskeleton, and the matrix affect rear retraction and linkage dissociation mechanisms. Our model also examines how applied forces and integrin clustering affect retraction kinetics. The model predicts two distinct detachment phenotypes. In the first, detachment is extremely rapid, dominated by integrin extracellular-matrix dissociation, and it occurs at high forces or low adhesiveness. In the second, detachment is much slower, dominated by integrin-cytoskeleton dissociation, and it occurs at low forces or high adhesiveness. The amount of integrin extracted from the rear of the cell is an assay for the detachment phenotype. During rapid detachment cells leave little integrin on the substratum whereas during slow detachment a large fraction of integrin rips from the membrane. This model delineates parameters which can be exploited to regulate cell speed in each detachment regime. The model also offers an explanation as to why some cell types, such as leukocytes or keratocytes, are able to detach easily and move very quickly while other cell types, such as fibroblasts, tend to migrate more slowly and release many more integrins during detachment. © 1999 Biomedical Engineering Society.

PAC99: 8717Jj, 8717Aa, 8715Rn, 8716Dg

Cell migration Rear retraction Integrins Cytoskeleton Extracellular matrix Calpain 

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Copyright information

© Biomedical Engineering Society 1999

Authors and Affiliations

  • Sean P. Palecek
    • 1
  • Alan F. Horwitz
    • 2
  • Douglas A. Lauffenburger
    • 1
    • 3
  1. 1.Department of Chemical EngineeringMassachusetts Institute of TechnologyCambridge
  2. 2.Department of Cell and Structural BiologyUniversity of Illinois at Urbana–ChampaignUrbana
  3. 3.Division of Bioengineering and Environmental Health and Center for Biomedical EngineeringMassachusetts Institute of TechnologyCambridge

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