Quantitative analysis of adhesion-mediated cell migration in three-dimensional gels of RGD-grafted collagen

Adhesion-mediated migration is required in a number of physiological and pa thological processes. A further quantitative understanding of the relations hip between cell migration and cell-substratum adhesiveness may aid in ther apeutic or tissue engineering applications. The aim of this work was to qua ntify three-dimensional cell migration as a function of increasing cell-sub stratum adhesiveness within reconstituted collagen gels. Cell-substratum ad hesiveness was controlled by grafting additional adhesive peptides containi ng the well-characterized arginine-glycine-aspartic acid sequence to collag en. The rkne-dimensional migration of multiple individual cells was tracked in real time in an automated fashion for extended periods. Cell displaceme nts were statistically analyzed and fit to a correlated persistent random w alk model to estimate root-mean-square speed, directional persistence time, and random motility coefficient. Based on model parameter estimates, cell speed was found to be a monotonically decreasing function of increasing sub stratum adhesiveness, while the directional persistence time and random mot ility coefficient exhibited a biphasic dependence, with maximum values at a pproximately intermediate concentrations of grafted adhesive peptide and he nce intermediate cell-substratum adhesiveness. In conclusion, these studies suggest an optimal adhesiveness for three-dimensional random migration, co nsistent with previous studies on two-dimensional surfaces. However, the ma ximum in random motility corresponded to a maximum in directional persisten ce, not in cell speed. (C) 2000 Biomedical Engineering Society: [S0090-6963 (00)05001-3].