Bt. Burgess et al., Quantitative analysis of adhesion-mediated cell migration in three-dimensional gels of RGD-grafted collagen, ANN BIOMED, 28(1), 2000, pp. 110-118
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].