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Computational Simulation of Mechanical Tests of Isolated Animal Cells
Bansod, Yogesh Deepak ; Kučera,, Ondřej (oponent) ; Florian, Zdeněk (oponent) ; Canadas, Patrick (oponent) ; Burša, Jiří (vedoucí práce)
A cell is complex biological system subjected to the myriad of extracellular mechanical stimuli. A deeper understanding of its mechanical behavior is important for the characterization of response in health and diseased conditions. Computational modeling can enhance the understanding of cell mechanics, which may contribute to establish structure-function relationships of different cell types in different states. To achieve this, two finite element (FE) bendo-tensegrity models of a cell in different states are proposed: a suspended cell model elucidating the cell’s response to global mechanical loads, such as elongation and compression and an adherent cell model explicating the cell’s response to local mechanical load, such as indentation using atomic force microscopy (AFM). They keep the central principles of tensegrity such as prestress and interplay between components, but the elements are free to move independently of each other. Implementing the recently proposed bendo-tensegrity concept, these models take into account flexural (buckling) as well as tensional behavior of microtubules (MTs) and also incorporate the waviness of intermediate filaments (IFs). The models assume that individual cytoskeletal components can change form and organization without collapsing the entire cell structure when they are removed and thus, can evaluate the mechanical contribution of individual cytoskeletal components to the cell mechanics. The suspended cell model mimics realistically the force-elongation response during cell stretching and the force-deformation response during cell compression, and both responses illustrate a non-linear increase in stiffness with mechanical loads. The simulation results demonstrate that actin filaments (AFs) and MTs both play a crucial role in defining the tensile response of cell, whereas AFs contribute substantially to the compressive response of cell. For adherent cell model, the force-indentation responses at two distinct locations are in accordance with the non-linear behavior of AFM experimental data. The simulation results exhibit that the indentation site dominates the cell behavior and for cell rigidity actin cortex (AC), MTs, and cytoplasm are essential. The proposed models provide valuable insights into the interdependence of cellular mechanical properties, the mechanical role of cytoskeletal components individually and synergistically, and the nucleus deformation under different mechanical loading conditions. Therefore, this thesis contributes to the better understanding of the cytoskeletal mechanics, responsible for cell behavior, which in turn may aid in investigation of various pathological conditions like cancer and vascular diseases.
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Computational Simulation of Mechanical Tests of Isolated Animal Cells
Bansod, Yogesh Deepak ; Kučera,, Ondřej (oponent) ; Florian, Zdeněk (oponent) ; Canadas, Patrick (oponent) ; Burša, Jiří (vedoucí práce)
A cell is complex biological system subjected to the myriad of extracellular mechanical stimuli. A deeper understanding of its mechanical behavior is important for the characterization of response in health and diseased conditions. Computational modeling can enhance the understanding of cell mechanics, which may contribute to establish structure-function relationships of different cell types in different states. To achieve this, two finite element (FE) bendo-tensegrity models of a cell in different states are proposed: a suspended cell model elucidating the cell’s response to global mechanical loads, such as elongation and compression and an adherent cell model explicating the cell’s response to local mechanical load, such as indentation using atomic force microscopy (AFM). They keep the central principles of tensegrity such as prestress and interplay between components, but the elements are free to move independently of each other. Implementing the recently proposed bendo-tensegrity concept, these models take into account flexural (buckling) as well as tensional behavior of microtubules (MTs) and also incorporate the waviness of intermediate filaments (IFs). The models assume that individual cytoskeletal components can change form and organization without collapsing the entire cell structure when they are removed and thus, can evaluate the mechanical contribution of individual cytoskeletal components to the cell mechanics. The suspended cell model mimics realistically the force-elongation response during cell stretching and the force-deformation response during cell compression, and both responses illustrate a non-linear increase in stiffness with mechanical loads. The simulation results demonstrate that actin filaments (AFs) and MTs both play a crucial role in defining the tensile response of cell, whereas AFs contribute substantially to the compressive response of cell. For adherent cell model, the force-indentation responses at two distinct locations are in accordance with the non-linear behavior of AFM experimental data. The simulation results exhibit that the indentation site dominates the cell behavior and for cell rigidity actin cortex (AC), MTs, and cytoplasm are essential. The proposed models provide valuable insights into the interdependence of cellular mechanical properties, the mechanical role of cytoskeletal components individually and synergistically, and the nucleus deformation under different mechanical loading conditions. Therefore, this thesis contributes to the better understanding of the cytoskeletal mechanics, responsible for cell behavior, which in turn may aid in investigation of various pathological conditions like cancer and vascular diseases.
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