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 pathological processes. A further quantitative understanding of the relationship between cell migration and cell-substratum adhesiveness may aid in therapeutic or tissue engineering applications. The aim of this work was to quantify three-dimensional cell migration as a function of increasing cell-substratum adhesiveness within reconstituted collagen gels. Cell-substratum adhesiveness was controlled by grafting additional adhesive peptides containing the well-characterized arginine-glycine-aspartic acid sequence to collagen. The three-dimensional migration of multiple individual cells was tracked in real time in an automated fashion for extended periods. Cell displacements were statistically analyzed and fit to a correlated persistent random walk 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 substratum adhesiveness, while the directional persistence time and random motility coefficient exhibited a biphasic dependence, with maximum values at approximately intermediate concentrations of grafted adhesive peptide and hence intermediate cell-substratum adhesiveness. In conclusion, these studies suggest an optimal adhesiveness for three-dimensional random migration, consistent with previous studies on two-dimensional surfaces. However, the maximum in random motility corresponded to a maximum in directional persistence, not in cell speed.
Burgess
B T
BT
University of Florida, Department of Chemical Engineering, Gainesville, USA.
Myles
J L
JL
Dickinson
R B
RB
D000818:Animals; D001698:Biomedical Engineering; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D003094:Collagen; D003470:Culture Media; D005782:Gels; D016023:Integrins / Q000502:physiology; D008546:Melanoma, Experimental / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D018715:Microscopy, Video; D009842:Oligopeptides; D014407:Tumor Cells, Cultured
D003470:Culture Media; D005782:Gels; D016023:Integrins; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D003094:Collagen