Impact of Stiffness and Cell-Binding Motif Availability on the Cell-Specific Response to Collagen-Based...

Although matrix stiffness is an important determinant of cell behavior, experimentally isolating mechanical cues from the surface chemistry is challenging. Here, intact collagen (Col I) or a constant density of collagen-derived cell-adhesive triple-helical peptides (GFOGER or GLOGEN) was deposited on surfaces with physiologically relevant stiffnesses. Equivalent integrin ligation on each surface decoupled stiffness from collagen-receptor ligation. The cell response was highly cell type-specific. Human dermal fibroblast (HDF) adhesion was largely insensitive to matrix stiffness, while cytoskeletal organization was promoted on stiffer substrates, equivalently for GFOGER and GLOGEN. Human umbilical vein endothelial cells (HUVECs) and human dermal microvascular endothelial cells (HDMECs) adhered and formed PECAM-1-containing cell-cell junctions preferentially on lower-modulus substrates. For HUVECs, this was independent of the coating peptide; however, HDMECs possessed greater PECAM-1-containing cell junctions on GFOGER over GLOGEN. These results offer new insights into the effects of stiffness vs integrin ligation on the cellular response to materials.