Finite element modeling of living cells for AFM indentation-based biomechanical characterization

Mechanotransduction-the process living cells sense and respond to forces-is essential for maintenance of normal cell, tissue, and organ functioning. To promote the knowledge of mechanotransduction, atomic force microscope (AFM) force-indentation has been broadly used to quantify the mechanical properties of living cells. However, most studies treated the cells as a homogeneous elastic or viscoelastic material, which is far from the real structure of cells, and the quantified mechanical properties cannot be used to investigate the inner working mechanism of mechanotransduction, such as internal force distribution/transduction. Therefore, a new viscoelastic finite element method (FEM) model is proposed in this study to simulate the force response of living cells during AFM force-indentation measurement by accounting for both the cell elasticity and viscoelasticity. The cell is modeled as a multi-layered structure with different mechanical characteristics of each layer to account for the depth-dependent mechanical behavior of living cells. This FEM model was validated by comparing the simulated force-indentation curves with the AFM experimental data on living NIH/3T3 cells, and the simulation error was less than 10% with respect to the experiment results. Therefore, the proposed FEM model can accurately simulate the force response of living cells and has a potential to be utilized to study and predict the intracellular force transduction and distribution.