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 nm 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.