Cell migration on cell-internalizable ligand microdepots: a phenomenological model

We have shown that collagen "ligand associated microdepots" (LAMs) at polymer substrates can significantly enhance levels of skin epidermal cell migration (Tjia and Moghe, Tissue Eng. 8:247-259, 2002). In this study, we have further examined the dynamics of cell-LAM interactions, primarily through a phenomenological model to examine the differential effects of LAM-cell binding and LAM internalization within the cells. Based on the experimental data of cell migration and LAM dynamics under selected conditions, the model was solved to yield rates of LAM binding and internalization at various LAM substrate densities. The clearance dynamics of LAMs computed at various times from the model matched well with the LAM clearance kinetics observed experimentally. The model was used to generate simulations of the rates of LAM binding and internalization over time, under conditions of differential exogenous activation. Our model analysis suggests that the rate of cell migration can be sensitively governed by rate of cellular sampling of LAMs, given by differential rates of LAM binding and internalization. Maximal cell migration was found to occur during LAM presentation regimes (LAM spatial density) that engendered concerted changes in the extent of cell activation, as measured via net tyrosine kinase activity, due to LAM sampling dynamics.