Single cell mechanical properties represent an increasingly studied descriptor for health and disease. Atomic force microscopy (AFM) has been widely used to measure single cell stiffness, despite its experimental limitations. The development of a computational framework to simulate AFM nanoindentation experiments could be a valuable tool to complement experimental findings. A single cell multi-structural finite element model was designed to this aim by using confocal images of bone cells, comprised of the cell nucleus, cytoplasm and actin cytoskeleton. The computational cell stiffness values were in the range of experimental values acquired on the same cells for nanoindentation of the cell nucleus and periphery, despite showing higher stiffness for the nucleus than for the periphery, oppositely to the average experimental findings. These results suggest it would be of interest to model different single cells with known experimental effective moduli to evaluate the ability of the computational models to replicate experimental results.