A model system involving a polyanionic alginic acid (AA) overlayer ionically immobilized on a polycationic polyethyleneimine underlayer, in turn linked to plasma oxidized polystyrene, was used to investigate the relationship between surface structure properties and resistance to cell adhesion. X-ray Photoelectron Spectroscopy (XPS) and water contact angle measurement were used to characterize the surfaces and to compare the results with data on resistance to adhesion of L-929 fibroblasts. A overlayer model was used to account for the XPS results in terms of fractional coverage by AA. Results show the strong effect of the surface density of AA chains on resistance to cell adhesion and underline the inadequacy of simple relationships between wettability by water and cell adhesion.