We developed a surface micropatterning technique to control the cell adhesion and protein adsorption. This micropatterned array system was fabricated by a photolithography technique and self-assembled monolayer (SAM) deposition. It was hypothesized that the wettability and functional terminal group would regulate cell adhesion and protein adsorption. To demonstrate this hypothesis, glass-based micropatterned arrays with various functional terminal groups, such as amine (NH2) group (3-aminopropyl-triethoxysilane, APT), methyl (CH3) group (trichlorovinylsilane, TVS), and fluorocarbon (CF3) group (trichloro(1H, 1H, 2H, 2H-perfluorooctyl)silane, FOTS), were used. The contact angle was measured to determine the hydrophilic and hydrophobic properties of materials, demonstrating that TVS and FOTS were hydrophobic, whereas APTs were relatively hydrophilic. The cell adhesion was significantly affected by the wettability, showing that the cells were not adhered to hydrophobic surfaces, such as TVS and FOTS. Thus, the cells were selectively adhered to glass substrates within TVS- and FOTS-based micropatterned arrays. However, the cells were randomly adhered to APTs-based micropatterned arrays due to hydrophilic property of APTs. Furthermore, the protein adsorption of the SAM-based micropatterned array was analyzed, showing that the protein was more absorbed to the TVS surface. The surface functional terminal group enabled the control of protein adsorption. Therefore, this SAM-based micropatterned array system enabled the control of cell adhesion and protein adsorption and could be a potentially powerful tool for regulating the cell-cell interactions in a well-defined microenvironment. Biotechnol. Bioeng. 2011;108: 1194-1202. (C) 2010 Wiley Periodicals, Inc.