Molecular engineering of cellular environments: cell adhesion to nano-digital surfaces.

Engineering of the cellular microenvironment has become a valuable means to guide cellular activities such as spreading, motility, differentiation, proliferation, or apoptosis. This chapter summarizes recent approaches to surface patterning such as topography and chemical patterning from the micrometer to the nanometer scale, and illustrates their application to cellular studies. Particular attention is devoted to nanolithography with self-assembled diblock copolymer micelles that are biofunctionalized with peptide ligands-a method that offers unsurpassed spatial resolution for the positioning of signaling molecules over extended surface areas. Such interfaces are defined here as "nano-digital surfaces," since they enable the counting of individual signaling complexes separated by a biologically inert background. The approach enables the testing of cellular responses to individual signaling molecules as well as their spatial ordering. Detailed consideration is also given to the fact that protein clusters such as those found at focal adhesion sites represent, to a large extent, hierarchically organized cooperativity among various proteins.