Biophys J, August 2002, p. 776-793, Vol. 83, No. 2

Reaction Diffusion Model of the Enzymatic Erosion of Insoluble Fibrillar Matrices

 ^*School of Computer Science and Engineering, and  ^#The Otto Loewi Minerva Center for Cellular and Molecular Neurobiology, Department of Neurobiology, Jerusalem 91904, Israel

Predicting the time course of in vivo biodegradation is a key issue in the design of an increasing number of biomedical applications such as sutures, tissue analogs and drug-delivery devices. The design of such biodegradable devices is hampered by the absence of quantitative models for the enzymatic erosion of solid protein matrices. In this work, we derive and simulate a reaction diffusion model for the enzymatic erosion of fibrillar gels that successfully reproduces the main qualitative features of this process. A key aspect of the proposed model is the incorporation of steric hindrance into the standard Michaelis-Menten scheme for enzyme kinetics. In the limit of instantaneous diffusion, the model equations are analogous to the standard equations for enzymatic degradation in solution. Invoking this analogy, the total quasi-steady-state approximation is used to derive approximate analytical solutions that are valid for a wide range of in vitro conditions. Using these analytical approximations, an experimental-theoretical method is derived to unambiguously estimate all the kinetic model parameters. Moreover, the analytical approximations correctly describe the characteristic hyperbolic dependence of the erosion rate on enzyme concentration and the zero-order erosion of thin fibers. For definiteness, the analysis of published experimental results of enzymatic degradation of fibrillar collagen is demonstrated, and the role of diffusion in these experiments is elucidated.

Biophys J, August 2002, p. 776-793, Vol. 83, No. 2
© 2002 by the Biophysical Society   0006-3495/02/08/776/18  $2.00