The effect of biological length scale topography on cell substrate adhesion in human corneal epithelial cells

The basement membrane underlying the corneal epithelium possesses a rich 3-dimensional nanoscale topography that may modulate cell-substrate adhesion. In this study, the effect of topography on cell-substrate adhesion was evaluated using a fluid shear detachment assay. We used lithographic techniques to create silicon substrates with anisotropic patterns in the form of uniform grooves and ridges and isotropic patterns in the form of cubic arrays of holes having length scales similar to those found in vivo.; SV40 human corneal epithelial cells (SV40-HCECs) cultured on the grooved silicon substrates for 24 hours exhibited an anisotropic morphological response in the form of contact guidance. Cells on the nanoscale holes possessed a stellate structure while cell spreading on the microscale holes and the planar surface was more rounded. When adherent cells were challenged to a nominal wall shear stress and cell detachment was monitored, we observed, within each feature type, that a statistically smaller proportion of cells detached from the biological length scale features, than on the microscale and planar topographies.; Analyses on how the shape response to topography influenced the measured adhesive response of cells to topography revealed that the shape of the cells did not have a significant impact on the ability of the cells to withstand a nominal wall shear stress. Furthermore, the results from our detachment assays support proposal that surface discontinuities are areas of enhanced cell substrate adhesion. Fluorescent microscopy of fibronectin indicates that the edges of the patterns may introduce local strains to the basal surface of the adherent cells that influence matrix secretion and organization and subsequently cell-substrate adhesion.; Nanoscale topography, with the same length scale as the basement membrane, significantly, enhances cell substrate adhesion and impacts other cell behaviors such as cell spreading, cell proliferation and the occurrence and extension of filopodia.