A new approach to control cell attachment using photochemistry and self-assembled monolayers (SAMs) has been developed. Poly(ethylene glycol) (PEG) was introduced onto a gold SAM surface to initially create a cell repulsive surface via a photo-cleavable o-nitrobenzyl functional group. This cell repulsive surface was subsequently rendered cell adhesive by exposure to UV-irradiation which cleaved the photoactive o-nitrobenzyl group, followed by immobilization of cell adhesive peptides to the irradiated regions. Water contact angle measurements, atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS) were used to confirm the photoreactions and to characterize surface properties. To study cell attachment on the prepared surfaces, NIH/3T3 fibroblast cells were used. The cell culture results demonstrated that PEG covered SAMs had the ability to repel cells and that the surface became cell adhesive after UV-irradiation to cleave cell non-adhesive PEG from the exposed surface via photo-labile o-nitrobenzyl groups, followed by immobilization of cell adhesive RGD peptides. In this study, we show that cell attachment can be controlled on photo-cleavable PEG-gold SAMs by UV exposure. We also show that the resulting surface is effective to control cell attachment for up to 5 days in culture. (C) 2010 Elsevier Inc. All rights reserved.