Fig. 8.

Proposed mechanism for human dermal fibroblast attachment and proliferation on collagen films. Initial attachment and spreading is predominantly driven by adhesion to integrin specific binding sites on the collagen film. Integrin-adherent cells then proceed to proliferate, with the rate driven by the stiffness of the underlying substrate. Where such motifs are engaged in crosslinking and unable to sustain the divalent metal cation needed for adhesion via the integrins, filopodia are extended to probe for substrate rigidity. Cells that have adhered to the surface in this manner, preferentially adhere to other cells. These cell clusters exert sufficient force to detach from the film surface, thus eventually undergoing apoptosis and lifting off the substrate surface.