A human hepatoma cell line (HepG2) was cultured on positively and negatively charged polyelectrolytes. Cell/surface adhesion and cell shape evolution were followed with quartz microbalance with dissipation (QCM-D) and optical microscopy as a function of time, respectively. In particular, substrates coated with poly(ethyleneimine) (PEI) led to fast cell attachment and further spreading, with average maximum frequency Deltaf = 79 Hz and dissipation DeltaD = 40 x 10(-6). On the contrary, no cell spreading was observed on poly(sodium-4-styrenesulfonate) (PSS), with Deltaf = 33 Hz and DeltaD = 4.5 x 10(-6). Atomic force microscopy (AFM) was used to investigate the influence of cell shape on its mechanical properties. Considering the cells as an homogenous solid material, the corresponding elastic modulus was estimated using the Hertz model. The elastic modulus was calculated at the central part of the cell, and the average values obtained were 191 +/- 14 Pa and 941 +/- 58 Pa for cells adsorbed on PSS and PEI, respectively. Thus, different cell-substrate interaction implied different cell mechanical properties reflected in a higher elastic modulus for stronger cell/substrate interaction. The combination of QCM-D, AFM, and optical microscopy allowed the online study of the cell adhesion process, and the mechanical properties of the adhered cells.