We employ simple geometrical rules to design a set of nanotopographies able to interfere with focal adhesion establishment during neuronal differentiation. Exploiting nanoimprint lithography techniques on cyclic-olefin-copolymer films, we demonstrate that by varying a single topographical parameter the orientation and maturation of focal adhesions can be finely modulated yielding independent control over the final number and the outgrowth direction of neurites. Taken together, this report provides a novel and promising approach to the rational design of biocompatible textured substrates for tissue engineering applications.