Nanosphere lithography (NSL) and the layer-by-layer (LbL) technique are combined here for the first time to design a flexible system to achieve nanotopographical control of cell adhesion. NSL is used to generate regular patterns of tetrahedral gold nanodots of different size and distance. Besides the change in topography, LbL is used to generate a polyelectrolyte multilayer (PEM) system consisting of heparin (HEP) and poly(ethylene imine) (PEI) on top of the gold dots. The localized formation of PEM on gold dots is achieved by prior passivation of the surrounding silicon or glass surface. Properties of PEM are changed by adjusting the pH value of HEP solution to either acidic or alkaline values. Studies with human dermal fibroblasts (HDF) reveal that cells spread to a higher extent on PEM formed at pH 5.0 in dependence on the structure dimension. Further, filopodia formation is highly increased in cells on nanostructures exhibiting HEP as a terminal layer. The new system offers a great potential to guide stem cell differentiation in the future owing to its high degree of chemical and topographical heterogeneity.
Keywords: fibroblast; heparin; nanolithography; patterning; poly(ethylene imine); polyelectrolyte; self-assembly.