On the determination of elastic moduli of cells by AFM based indentation.

The atomic force microscopy (AFM) has been widely used to measure the mechanical properties of biological cells through indentations. In most of existing studies, the cell is supposed to be linear elastic within the small strain regime when analyzing the AFM indentation data. However, in experimental situations, the roles of large deformation and surface tension of cells should be taken into consideration. Here, we use the neo-Hookean model to describe the hyperelastic behavior of cells and investigate the influence of surface tension through finite element simulations. At large deformation, a correction factor, depending on the geometric ratio of indenter radius to cell radius, is introduced to modify the force-indent depth relation of classical Hertzian model. Moreover, when the indent depth is comparable with an intrinsic length defined as the ratio of surface tension to elastic modulus, the surface tension evidently affects the indentation response, indicating an overestimation of elastic modulus by the Hertzian model. The dimensionless-analysis-based theoretical predictions, which include both large deformation and surface tension, are in good agreement with our finite element simulation data. This study provides a novel method to more accurately measure the mechanical properties of biological cells and soft materials in AFM indentation experiments.