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Computational Simulation of Mechanical Behaviour of Endothelial Cells
Jakka, Veera Venkata Satya ; Gumulec, Jaromír (oponent) ; Majer, Zdeněk (oponent) ; Matsumoto,, Takeo (oponent) ; Burša, Jiří (vedoucí práce)
Atherogenesis is the leading cause of death in the developed world, and is putting considerable monetary pressure on health systems the world over. The prevailing haemodynamic environment together with the local concentration of mechanical load play an important role in the focal nature of atherosclerosis to very specific regions of the human vasculature. In blood vessels, the endothelium, a thin monolayer of cells, lies at the interface between the bloodstream and the vascular wall. Dysfunction of endothelial cells is involved in major pathologies. For instance, atherosclerosis develops when the barrier and anti-inflammatory functions of the endothelium are impaired, allowing accumulation of cholesterol and other materials in the arterial wall. In cancer, a key step in the growth of a tumour is its vascularization, a process driven by endothelial cell migration. The mechanical environment of endothelial cells plays a key role in their function and dysfunction. Computational modelling can enhance the understanding of cell mechanics, which may contribute to establishing structure-function relationships of different cell types in different states. To achieve this, finite element (FE) models of endothelium cell are proposed in this thesis, i.e. a suspended cell model and adherent model elucidating the cell’s response to global mechanical loads, such as tension and compression, as well as a model of the cell with its natural shape inside the endothelial layer. They keep the central principles of tensegrity such as prestress and interplay between components, but the elements are free to rearrange independently of each other. Implementing the recently proposed bendo-tensegrity concept, these models consider flexural (buckling) as well as tensional/compressional behaviour of microtubules (MTs) and also incorporate the waviness of intermediate filaments (IFs). The models assume that the individual cytoskeletal components can change their form and organization without collapsing the entire cell structure when they are removed and thus, they enable us to evaluate the mechanical contribution of individual cytoskeletal components to the cell mechanics. The proposed models are validated with experimental results by comparison of their force-displacement curves. The suspended cell model mimics realistically the force-deformation responses during cell stretching and compression, and both responses illustrate a non-linear increase in stiffness with mechanical loads. The compression test of flat endothelial cell is simulated and compared with adherent cell test and its simulation. Then, the shear test of flat cell is simulated to assess its shear behaviour occurring in vascular wall due to blood flow. Then investigated the mechanical response of the flat cell within the endothelium layer under physiological conditions in arterial wall. Later, investigated the cell response in debonding during cyclic stretches using 3-D finite element simulations. The proposed models provide valuable insights into the interdependence of cellular mechanical properties, the mechanical role of cytoskeletal components in endothelial cells individually and synergistically, and the nucleus deformation under different mechanical loading conditions. Therefore, the thesis should contribute to the better understanding of the cytoskeletal mechanics, responsible for endothelial cell behaviour, which in turn may aid in investigation of various pathological conditions related to
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