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Evaluation of elastic parameters for models of isolated cells
Krbálek, Jaroslav ; Fuis, Vladimír (referee) ; Burša, Jiří (advisor)
This diploma thesis focuses on computational modeling of the cell mechanical tests. The goal of this thesis is to build a cell model and to simulate compression test on this model. If necessary, the model should be adjusted so the model reflects real cell behavior. It was created the cell model reflecting cytoplasm, nucleus, membrane and cell cytoskeleton. Cytoskeleton was modeled as tensegrity structure. After this, the pressure test was simulated on this model. The behavior of the cell model and real cell was compared using the stress force. The stress force - cell deformation curve was markedly different for the cell model and the real cell. For this reason, the cytoplasm material model was adjusted. The difference between the curves was acceptable after this modification. It was found during computations that the cytoskeleton model influence on the cell load is minimal. These results does not reflects real cell behavior, which means that the model is considered inadequate for performing stress load simulation.
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Application of tensegrity structures in modelling of mechanical behaviour of smooth muscle cells
Bauer, David ; Fuis, Vladimír (referee) ; Burša, Jiří (advisor)
The master’s thesis deals with the computational modelling of the mechanical testing of isolated smooth muscle cells. The main aims are to create computational model of a cell, to simulate single-axis tensile test and to modify the model so that the model reflects real mechanical response. The model of the cell includes cytoplasm, nucleus, cell membrane and cytoskeleton which is modelled as a tensegrite structure. On this model the tensile test was simulated in case of the cell with cytoskeleton and the cell with distributed the cytoskeleton. Force-elongation curves, which were obtained from this simulation, were compared with experimental data which were taken from literature. Tensile properties were measured on freshly isolated cells from rat thoracic aorta, cultured cells, and cells treated with cytochalasin D to disrupt their actin filaments. It was found that the cytoskeleton influence on the cell load in computational model was smaller than in the real cell. Therefore the model was modified by changing material propreties and geometry so that the model of the cell corresponded with the different types of experimentally measured cells.
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Vplyv vybraných endokrinných disruptorov na metabolismus lipidov v pečeňových bunkových modeloch
Konopová, Veronika
Endocrine Disrupting Compounds (EDCs) are exogenous compounds that interfere with the endocrine system and consequently elicit toxic outcomes. One of their possible consequences in the organism is their negative impact on metabolic processes linked with development of metabolic diseases, including liver steatosis. In this research area, it is important to develop suitable in vitro cellular models. In this thesis, we evaluated the possibility of using of cell model of immortalized human hepatocytes, MIHA cell line, for detection of activation of nuclear receptors, PXR, LXRa a PPARa, which might be targeted by some EDC. We studied in particular the induction of expression of target genes of these receptors, CYP3A4, SCD, PDK4, CPTT1A, with the aim to compare the sensitivity of MIHA cells with a commonly used of liver cells, HepaRG cell line. The results showed that although some EDC (or model ligands of nuclear receptors) may induce the expression of target genes of nuclear receptors in MIHA cells, in general, this cell model appears to be less suitable for studying the impact of EDC than HepaRG cell line. The MIHA cell line, though, allows to study the compounds activating PPARa, which is an important regulator of metabolism of fatty acids in the liver tissue.
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Preparation and characterization of cell models of lysosomal hereditary diseases - Mucopolysaccharidoses
Presová, Gabriela ; Dobrovolný, Robert (advisor) ; Dvořáková, Lenka (referee)
Mucopolysaccharidoses are a group of diseases that belong to lysosomal storage disorders. A common sign of these monogenic multisystem diseases is a gene mutation leading to a deficiency of the lysosomal enzyme participating in glycosaminoglycan degradation. It results to their accumulation in the tissues and organs, where they cause a progressive damage. There is no efficient treatment available for most mucopolysaccharidoses. Moreover, the research is complicated because of the low prevalence and type of affected tissues. Animal models of these human diseases are used for an evaluation of newly developed therapeutic approaches. However, they also have many limitations due to the different pathogenesis and catabolic pathways of the accumulated substrates between humans and animals. Therefore, animal models are replaced by human cell models. In this thesis, the development of four mucopolysaccharidoses human cell models is reported (MPS IIID, MPS IVA, MPS IVB, MPS VI). Corresponding genes (GNS, GALNS, GLB1, ARSB) were inactivated using CRISPR/Cas9 technology, where plasmids containing specific inserts are delivered to the target human induced pluripotent stem cells (iPSC), using electroporation. Isolated clones, which represent iPSC disease models, were characterized by Sanger sequencing, enzyme...
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Application of tensegrity structures in modelling of mechanical behaviour of smooth muscle cells
Bauer, David ; Fuis, Vladimír (referee) ; Burša, Jiří (advisor)
The master’s thesis deals with the computational modelling of the mechanical testing of isolated smooth muscle cells. The main aims are to create computational model of a cell, to simulate single-axis tensile test and to modify the model so that the model reflects real mechanical response. The model of the cell includes cytoplasm, nucleus, cell membrane and cytoskeleton which is modelled as a tensegrite structure. On this model the tensile test was simulated in case of the cell with cytoskeleton and the cell with distributed the cytoskeleton. Force-elongation curves, which were obtained from this simulation, were compared with experimental data which were taken from literature. Tensile properties were measured on freshly isolated cells from rat thoracic aorta, cultured cells, and cells treated with cytochalasin D to disrupt their actin filaments. It was found that the cytoskeleton influence on the cell load in computational model was smaller than in the real cell. Therefore the model was modified by changing material propreties and geometry so that the model of the cell corresponded with the different types of experimentally measured cells.
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Evaluation of elastic parameters for models of isolated cells
Krbálek, Jaroslav ; Fuis, Vladimír (referee) ; Burša, Jiří (advisor)
This diploma thesis focuses on computational modeling of the cell mechanical tests. The goal of this thesis is to build a cell model and to simulate compression test on this model. If necessary, the model should be adjusted so the model reflects real cell behavior. It was created the cell model reflecting cytoplasm, nucleus, membrane and cell cytoskeleton. Cytoskeleton was modeled as tensegrity structure. After this, the pressure test was simulated on this model. The behavior of the cell model and real cell was compared using the stress force. The stress force - cell deformation curve was markedly different for the cell model and the real cell. For this reason, the cytoplasm material model was adjusted. The difference between the curves was acceptable after this modification. It was found during computations that the cytoskeleton model influence on the cell load is minimal. These results does not reflects real cell behavior, which means that the model is considered inadequate for performing stress load simulation.
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