The goal of this study is to construct a representative 3D finite element model of a biological cell based on the sub-cellular structures that provide the cell with its mechanical properties. The geometries for the model are constructed from 3D microscope images of cells using proprietary analytical algorithms, imported into Patran for pre-processing, and submitted to Marc for analysis. Vascular smooth muscle cells (VSMCs) are chosen for the study due to the strong correlation of the geometric arrangement of their structural components on their mechanical behavior and the implications of that behavior on diseases such as atherosclerosis.
The ability to model the mechanical responses of cells to physical stimuli presents many opportunities to the world of medical research. Chief among these is the ability to further our understanding of the etiology of many diseases. There are a wide variety of diseases whose etiology or clinical presentation are either known or suspected to be related to abnormal cellular mechanics, alteration of the cellular processes that regulate transmission of mechanical stimuli into biochemical responses, or changes in tissue structure. Because physical distortion can affect cell how cells grow, specialize themselves for specific tasks, move, and whether they live or die, the ability to predict the mechanical behavior of cells in response to pathological conditions and medical treatments may be critical to prevention and treatment of many of these diseases.
VSMCs are modeled here using a linear elastic material model together with truss elements in Marc which simulate the cytoskeletal fiber network that provides the cells with much of their internal structural support. Geometric characterization of single VSMCs in 2D cell culture is achieved using confocal microscopy in conjunction with novel image processing techniques. These techniques allow for the creation of representative 3D model structures consisting of the cell nucleus, cytoplasm, and actin stress fiber network of each cell, which are then imported into Patran for structural analysis with Marc. Mechanical characterization is achieved using atomic force microscopy (AFM) indentation and stress relaxation techniques. Material properties for each VSMC model are input based on values individually obtained through experimentation, and the results of each model are compared against those experimental values.
This study is believed to be a significant step towards the viability of finite element models in the field of cellular mechanics because the geometries of the cells in the model are based on confocal microscopy images of actual cells with mechanical data obtained immediately prior to imaging and thus, the results of the model can be compared against experimental data for those same cells. These types of models could one day be used to decrease the cost and speed the development of new drug discovery and regenerative medicine therapies, as well as increase our understanding of the relationship between the structure and function of biological cells.
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