Atomic force microscopy-based single-cell indentation: Experimentation and finite element simulation

In order to understand and characterize the mechanical property and response of the mouse embryonic stem cells (mESC), we used an atomic force microscope (AFM) combined with a PHANToM haptic feedback device. Atomic force microscopy has rapidly become a valuable tool for quantifying the biophysical properties of single cells or a collection of cells through force measurements. We report herein the mechanical characterization of single mESC using indentation-relaxation measurements with micro-sphere AFM probes for fixed and live undifferentiated mESC. During cell indentation for both live and fixed undifferentiated cells, we provided force feedback to the user in real-time through the PHANToM haptic feedback device as the AFM tip was deforming the cell. The force was amplified for the human operator to perceive the change in force during cell indentation by the AFM cantilever. This information can be used as a mechanical marker to characterize state of the cell (live and fixed). As the interpretation of atomic force microscopy-based indentation tests is highly dependent on the use of an appropriate theoretical model of the testing configuration, various contact models are presented to predict the mechanical behavior of an individual mouse embryonic stem cells (mESC) in different states. A comparison study with finite element simulations (FEM) of spherical tip indentation demonstrates the effectiveness of our computational model to predict the mESC deformation during indentation and relaxation nanomanipulation tasks.