To investigate the response of human epithelial cells to substrates with nanoscale modifications, dendrimer-immobilized surfaces were prepared with or without D-glucose displayed as a terminal ligand, giving topographic structures with mean roughnesses (R-a) of 1.8-11.0 nm. With an increase in the R-a value up to 4.0 nm, the epithelial cells cultured on naked dendrimer surface without D-glucose display were somewhat stretched in their morphology compared with those on a nonmodified plain surface. However, for the R-a, values higher than 4.0 nm, such cell stretching was inhibited, resulting in the predominant existence of round-shaped cells. The change in cell morphology was appreciable on the surfaces with D-glucose-displayed dendrimers. When the R-a value increased up to 4.5 urn on these surfaces, in particular, the enhancement of cell stretching was recognized, and fluorescence microscopic observation supported the hypothesis that the glucose-transporter-mediated adhesion of cells to the surface encouraged the development of filopodia and stress fibers, thereby improving focal contact with the surface. Our results suggest that the combination of displaying D-glucose and modulating roughness can promote cytoskeletal formation accompanied by marked cell elongation on culture surfaces.