The ability of electrostatically driven layer-by-layer (LbL) assembly to adapt to the morphological features of a template was explored. Subtle cytoskeletal changes in blood platelets became traceable through energy dissipation monitoring in multilayered shells using microgravimetric measurements. This LbL coating was sequentially deposited on protein-modified chips onto which platelets were adhered. In addition to consequently improving the signal sensitivity, the LbL shell acted in synergy with the cell, allowing the determination and quantification of cytoskeletal changes induced by the specific cell adhesion to the protein-modified chip surface used with a quartz crystal microbalance with dissipation. The difference in cell morphology, as a result of the optimization of specific interactions between the protein layer and cell membrane integrins induced viscoelastic changes in the polyelectrolyte shell, thereby providing quantitative data on platelet conformational changes upon their adhesion to protein-modified chip surface.