In this paper we report a method for biomaterial surface modification that utilizes the self-assembly of block copolymers of poly(styrene-block-ethylene oxide) (PS-PEO) to generate micro-phase separated surfaces with varying density PEO domains. These PS-PEO self-assembled surfaces showed a significant reduction in protein adsorption compared to control polystyrene surfaces. The adhesion of NIH-3T3 fibroblast cells was shown to be significantly affected by the surface coverage of PEO nano-domains formed by copolymer self-assembly. These nano-domains, when presented at high number density (almost 1000 domains per square micron), were shown to completely prevent cellular attachment, even though small amounts of protein were able to bind to the surface.