Epidermal growth factor (EGF) is a growth factor that binds a cell surface receptor to an EGF receptor, to promote cell growth and proliferation. The results of quartz crystal microbalance with dissipation (QCM-D) continuous monitoring for 100 min after stimulation with EGF of dosages confirmed that the energy dissipation decreases over time. Fatomic force microscopy (AFM) performs nanoindentation on cell membranes with less than 500 nm deformation in a single-cell analysis fashion revealing cell cytoplasm properties, while QCM-D monitors the cell–extracellular matrix interfacial layer where focal adhesion dominates the energy dissipation. Therefore, AFM and QCM-D work in a complementary manner in the characterization of the changes in viscoelastic properties of the cell. Cell signaling is one of the fundamental processes that control cell fate. Knowledge of the changes in mechanical properties will provide with more insight into the dynamics of cell signaling.