Construction and simulation-experimental characterization of a fluorescence image-based finite element model for cell mechanics.

OBJECTIVE: A finite element (FE) model was developed to characterize the three-dimensional (3D) heterogeneous structure features of cells, and the influence mechanism of cytoskeleton remodeling on the mechanical properties of cells and the intracellular stress transmission behavior was analyzed. METHODS: Human lung adenocarcinoma A549 cells were used in this study, and the cytoskeleton model was constructed by using cytochalasin D (Cyto-D) at concentrations of 0, 0.1, and 1.0 μmol/L. Based on the 3D fluorescence image stacks obtained by confocal laser scanning microscopy (CLSM), combined with the image processing algorithm written in MATLAB, the 3D surface structure of the cells was reconstructed. Atomic force microscopy (AFM) was used to perform nanoindentation experiments to characterize the mechanical parameters of the cells. A multi-body contact FE model of "probe-cytoskeleton-nucleus-culture dish" was constructed based on the ANSYS platform, and the stress distribution and mechanical response of cells under indentation loading were simulated on this basis. RESULTS: With the increase of Cyto-D concentration, the AFM nanoindentation showed that the cell height significantly decreased, while the Young's modulus and adhesion force increased (p < 0.05). The FE simulation showed an approximately linear stress-strain relationship during the probe displacement loading. The image-based cell models exhibited obvious structural dependence, demonstrating non-uniform and asymmetric mechanical transmission. The deformation, strain, and stress levels of the nucleus were lower than those of the cytoskeleton region, but it still participated in progressive force transmission, forming a continuous gradient. There was no abrupt mechanical response at the nucleus-cytoskeleton interface, but a smooth transition, indicating that this interface had a certain buffering effect on the load and helped maintain the stability of the internal structure of the cells. With the increase of Cyto-D concentration, the simulation results of the model changed from local concentration to directional expansion and finally developed into a diffuse distribution. These findings suggest that the cytoskeleton disassembly process dominated the changes in the mechanical behavior of the cells. CONCLUSION: The proposed framework provides a feasible approach for integrating fluorescence imaging with FE analysis in cell mechanics research and may serve as a methodological reference for studying the relationship between cytoskeletal organization and cellular mechanical behavior.