The thermodynamics of cell adhesion are regulated by the conformation, energetics and dynamics of adhesion receptors. In addition, clustering of these receptors regulates adhesion as well as downstream signaling. In this Letter, we present an integrated model incorporating Monte Carlo simulations and a mean field approach to study the effect of receptor clustering on free energy of cell adhesion. The Monte Carlo simulation incorporates receptor diffusion and dimerization and provides input for the mean field computation of free energy of adhesion in a receptor-ligand-solvent system. Our results show that cell adhesion is regulated by high co-operativity and synergy between receptor density and interaction energy. (c) 2008 Published by Elsevier B.V.