Apoptosis is the process of programmed cell death that occurs in multi-cellular organisms. The apoptosis process of animal cells is characterized by a series of changes on the cell body such as loss of membrane symmetry, cell shrinkage, chromatin condensation and DNA fragmentation. Apoptosis is of great importance as a cellular process, whereas the malfunction of which would lead to a variety of disease including cancer. In a potential fatal skin disease pemphigus vulgaris (PV), it is found that auto-immune antibody will induce the apoptosis of keratinocytes, the main epithelial cell that forms the skin, resulting in the blistering of the skin. The exact mechanism of apoptosis in PV is not well understood. Atomic force microscopy (AFM), originally invented as a high resolution imaging tool, recently finds wide applications in biological science with its unique properties. It can operate in liquid where physiological conditions for biological matters can be kept, which makes it an ideal tool for structural characterization of live cells. Besides, it is a natural nanoindenter with high sensitivity and can both measure and apply extremely small forces. Furthermore, the AFM-based nanomanipulation system makes it even more convenient to change things in the molecular level. By applying the AFM-based nanorobotic system to the cellular model system in PV via statistical analysis of nanoindentation data obtained in real time combined with high resolution structural characterization, we find that the cells become stiffer when apoptosis early process begin. This methodology and technique will facilitate the diagnosis and treatment of PV in the future.