Oscillatory behavior of a simple kinetic model for proteolysis during cell invasion.
Extracellular proteolysis during cell invasion is thought to be tightly organized, both temporally and spatially. This work presents a simple kinetic model that describes the interactions between extracellular matrix (ECM) proteins, proteinases, proteolytic fragments, and integrins. Nonmonotonous behavior arises from enzyme de novo synthesis consecutive to integrin binding to fragments or entire proteins. The model has been simulated using realistic values for kinetic constants and protein concentrations, with fibronectin as the ECM protein. The simulations show damped oscillations of integrin-complex concentrations, indicating alternation of maximal adhesion periods with maximal mobility periods. Comparisons with experimental data from the literature confirm the similarity between this system behavior and cell invasion. The influences on the system of cryptic functions of ECM proteins, proteinase inhibitors, and soluble antiadhesive peptides were examined. The first critical parameter for oscillation is the discrepancy between integrin affinity for intact ECM proteins and the respective proteolytic fragments, thus emphasizing the importance of cryptic functions of ECM proteins in cell invasion. Another critical parameter is the ratio between proteinase and the initial ECM protein concentration. These results suggest new insights into the organization of the ECM degradation during cell invasion.
Berry
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H
ERRMECE, University of Cergy-Pontoise, 95302 Cergy-Pontoise Cedex, France.
Larreta-Garde
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D000204:Activity Cycles / Q000502:physiology; D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D002465:Cell Movement / Q000502:physiology*; D010450:Endopeptidases / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000502:physiology; D005353:Fibronectins / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000502:physiology; D007700:Kinetics; D008024:Ligands; D008954:Models, Biological; D009842:Oligopeptides / Q000502:physiology; D009991:Oscillometry; D011480:Protease Inhibitors / Q000378:metabolism
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D016023:Integrins; D008024:Ligands; D009842:Oligopeptides; D011480:Protease Inhibitors; C047981:arginyl-glycyl-aspartic acid; D010450:Endopeptidases