Multidepth quantitative analysis of liver cell viscoelastic properties: Fusion of nanoindentation and finite element modeling techniques

Liver cells are the basic functional unit of the liver. However, repeated or sustained injury leads to structural disorders of liver lobules, proliferation of fibrous tissue and changes in structure, thus increasing scar tissue. Cellular fibrosis affects tissue stiffness, shear force, and other cellular mechanical forces. Mechanical force characteristics can serve as important indicators of cell damage and cirrhosis. Atomic force microscopy (AFM) has been widely used to study cell surface mechanics. However, characterization of the deep mechanical properties inside liver cells remains an underdeveloped field. In this work, cell nanoindentation was combined with finite element analysis to simulate and analyze the mechanical responses of liver cells at different depths in vitro and their internal responses and stress diffusion distributions after being subjected to normal stress. The sensitivities of the visco-hyperelastic parameters of the finite element model to the effects of the peak force and equilibrium force were compared. The force curves of alcohol-damaged liver cells at different depths were measured and compared with those of undamaged liver cells. The inverse analysis method was used to simulate the finite element model in vitro. Changes in the parameters of the cell model after injury were explored and analyzed, and their potential for characterizing hepatocellular injury and related treatments was evaluated. RESEARCH HIGHLIGHTS: This study aims to establish an in vitro hyperelastic model of liver cells and analyze the mechanical changes of cells in vitro. An analysis method combining finite element analysis model and nanoindentation was used to obtain the key parameters of the model. The multi-depth mechanical differences and internal structural changes of injured liver cells were analyzed.