The primary objective of this study is to investigate the interactive forces that promote the adsorption of bio-conjugated nanoparticles onto proteins. To elucidate the interactive forces, we demonstrate an approach using synthetic and model biological surfaces to study adsorption of bio-conjugated nanopartides. Real-time adsorption of BSA conjugated silver nanoparticles (Ag/BSA NPs) on the immobilized substrates was followed by surface plasmon resonance (SPR). The extent of adsorption of the nanoparticles on the synthetic surface was found to be larger for self-assembled monolayers (SAMs) with unionizable terminal groups and lower for SAMs with unionizable terminal groups. For model biological substrate, the extent of nanoparticles adsorption was found to relate to the plc of immobilized proteins. For collagen immobilized substrate, the adsorption of Ag/BSA nanoparticles showed a significantly higher SPR response than that of free BSA. The extent of nanoparticles adsorption on the collagen immobilized substrate was also influenced by the type and concentration of electrolyte used in dispersing nanoparticles. Our findings indicate that the adsorption of nanoparticles to immobilized surface has contributions from electrostatic interactions, hydrophobic, and/or hydrogen bonding. This work provides the framework to study interactions that may arise when bio-conjugated nanoparticles are transported in biological systems. (C) 2013 Elsevier Inc. All rights reserved.