Abstract
The stiffness of cells, especially cancer cells, is a key mechanical property that is closely associated with their biomechanical functions, such as the mechanotransduction and the metastasis mechanisms of cancer cells. In light of the low survival rate of single cells and measurement uncertainty, the finite element method (FEM) was used to quantify the deformations and predict the stiffness of single cells. To study the effect of the cell components on overall stiffness, two new FEM models were proposed based on the atomic force microscopy (AFM) indentation method. The geometric sizes of the FEM models were determined by AFM topography images, and the validity of the FEM models was verified by comparison with experimental data. The effect of the intermediate filaments (IFs) and material properties of the cellular continuum components on the overall stiffness were investigated. The experimental results showed that the stiffness of cancer cells has apparent positional differences. The FEM simulation results show that IFs contribute only slightly to the overall stiffness within 10% strain, although they can transfer forces directly from the membrane to the nucleus. The cytoskeleton (CSK) is the major mechanical component of a cell. Furthermore, parameter studies revealed that the material properties (thickness and elasticity) of the continuum have a significant influence on the overall cellular stiffness while Poisson's ratio has less of an influence on the overall cellular stiffness. The proposed FEM models can determine the contribution of the major components of the cells to the overall cellular stiffness and provide insights for understanding the response of cells to the external mechanical stimuli and studying the corresponding mechanical mechanisms and cell biomechanics.
Highlights
Cell stiffness has an important influence on the cell biomechanical functions of cells and the mechanisms of mechanotransduction, such as cell motility, pathophysiology, and metastasis mechanisms of cancer cells [1]
E developed finite element method (FEM) models are verified by selecting two indentation points, point 1 and point 4 (3/4 of the major diameter from the cell centre), which are chosen according to the experimental measurement positions. e force-indentation curves are demonstrated in Figure 4, where the black lines represent the experimental data and the red lines represent the simulation data
It is widely accepted that intermediate filaments (IFs) have a key role in cell mechanics [15]. e effect of IFs on overall cellular stiffness within the small deformation state was investigated. e results showed that IFs contribute only slightly to the overall cellular stiffness, as shown in Figure 5, which was consistent with the published conclusions [20, 21]
Summary
Cell stiffness has an important influence on the cell biomechanical functions of cells and the mechanisms of mechanotransduction, such as cell motility, pathophysiology, and metastasis mechanisms of cancer cells [1]. Cross et al [6] used the AFM indentation methods to measure Young’s modulus of live metastatic cancer cells taken from pleural effusions of patients. Hayashi and Iwata [9] used the same technique to study the stiffness of HeLa cells and End1/E6E7 at different locations. The mechanical properties such as the stiffness, elasticity, and viscoelasticity of cells were studied mainly through experimental methods. FEM modelling of cells is favoured by researchers in the field of cellular mechanics. Chen and Lu [10] conducted a 2D model for AFM nanoindentation on chondrocytes by assuming the cells to be a homogeneous
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