Biocompatible, ultrathin coatings on silicon substrates are of tremendous interest for the development of silicon-based miniature biodevices, such as biosensors and interfaces with neurons. We have developed a practical method for preparing monolayers presenting oligo(ethylene glycol)s (OEG) on silicon surfaces. These monolayers are the most protein-resistant and stable monolayers reported to date. We have also incorporated ethynyl groups on the films for attaching biomoleucles with an azido group through “click reaction”. Further, we have made progress on the fabrication of single molecule patterns presenting adhesion and signaling molecules on the OEG platforms. The perspectives of using these model systems to control the nanoscale patterns of intracellular molecular assemblies and to study their influences on the signal transduction and cellular response will be presented.