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

Fibrin-based interpenetrating polymer network biomaterials with tunable biodegradability

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Enzyme-Catalyzed Gel Proteolysis: An Anomalous Diffusion-Controlled Mechanism

Enzyme-catalyzed proteolysis of gelatin gels has been studied. We report a gel degradation rate varying as the square of the enzyme concentration. The diffusion motion of enzymes in the gel has been measured by two-photon fluorescence correlation spectroscopy and identified as being anomalously slow. These experimental results are discussed from a theoretical point of view and interpreted in terms of a diffusion-controlled mechanism for the gel degradation. These results make a step toward the understanding of enzyme-catalyzed gel degradation and give new insight on biological processes such as the action of metalloproteinases in the extracellular matrix involved in cellular invasion