No description available.

Cell shape is important to understanding the mechanics of three-dimensional (3D) cell aggregates. When an aggregate of embryonic cells is compressed between parallel plates, the cell mass and the cells of which it is composed flatten. Over time, the cells typically move past one another and return to their original, spherical shapes, even during sustained compression, although the profile of the aggregate changes little once plate motion stops. Although the surface and interfacial tensions of cells have been attributed to driving these internal movements, measurements of these properties have largely eluded researchers. Here, an existing 3D finite element model, designed specifically for the mechanics of cell-cell interactions, is enhanced so that it can be used to investigate aggregate compression. The formulation of that model is briefly presented and enhancements made to its rearrangement algorithms discussed. Simulations run using the model show that the rounding of interior cells is governed by the ratio between the interfacial tension and cell viscosity, whereas the shape of cells in contact with the medium or the compression plates is dominated by their respective cell-medium or cell-plate surface tensions. The model also shows that as an aggregate compresses, its cells elongate more in the circumferential direction than the radial direction. Since experimental data from compressed aggregates are anticipated to consist of confocal sections, geometric characterization methods are devised to quantify the anisotropy of cells and to relate cross sections to 3D properties. The average anisotropy of interior cells as found using radial cross sections corresponds more closely with the 3D properties of the cells than data from series of parallel sections. A basis is presented for estimating cell-cell interfacial tensions from the cell shape histories they exhibit during the cell reshaping phase of an aggregate compression test.

Cell shape is important to understanding the mechanics of three-dimensional (3D) cell aggregates. When an aggregate of embryonic cells is compressed between parallel plates, the cell mass and the cells of which it is composed flatten. Over time, the cells typically move past one another and return to their original, spherical shapes, even during sustained compression, although the profile of the aggregate changes little once plate motion stops. Although the surface and interfacial tensions of cells have been attributed to driving these internal movements, measurements of these properties have largely eluded researchers. Here, an existing 3D finite element model, designed specifically for the mechanics of cell-cell interactions, is enhanced so that it can be used to investigate aggregate compression. The formulation of that model is briefly presented and enhancements made to its rearrangement algorithms discussed. Simulations run using the model show that the rounding of interior cells is governed by the ratio between the interfacial tension and cell viscosity, whereas the shape of cells in contact with the medium or the compression plates is dominated by their respective cell-medium or cell-plate surface tensions. The model also shows that as an aggregate compresses, its cells elongate more in the circumferential direction than the radial direction. Since experimental data from compressed aggregates are anticipated to consist of confocal sections, geometric characterization methods are devised to quantify the anisotropy of cells and to relate cross sections to 3D properties. The average anisotropy of interior cells as found using radial cross sections corresponds more closely with the 3D properties of the cells than data from series of parallel sections. A basis is presented for estimating cell-cell interfacial tensions from the cell shape histories they exhibit during the cell reshaping phase of an aggregate compression test.

In this thesis, I present a detailed analysis of the role cell morphology, solution rheology, and swimming mechanism has on the motility of Helicobacter Pylori. H. Pylori, the bacterium that causes gastric ulcers, has a helical cell shape that has long been believed to provide an advantage in penetrating the viscous mucus layer protecting the stomach lining, its niche environment. I present results obtained by performing optical microscopic live cell bacteria tracking of wild-type H. Pylori and cell shape and flagella mutants of H. Pylori. Bacteria tracking experiments show that helical shaped bacteria swim faster than straight rod-shaped bacteria, and bacteria with larger number of flagella swim faster. Altering cell shape is found to have a smaller effect on swimming speed than altering the number of flagella a bacterium has. These experimental observations are then compared to resistive force theory predictions. Resistive force theory shows qualitative agreement to our experimental observations, but overestimates the increase in swimming speed for a helical cell when compared to straight rod cell. In addition to effect of cell morphology on motility, I explore how motility is altered in different polymer environments by tracking bacteria in pig gastric mucin, methylcellulose, and gelatin solutions and gels. Bacteria are found to increase their swimming speed non-monotonically with increasing polymer concentration, while the number of mobile bacteria is found to decrease with increased polymer concentration. I also present an analysis of the swimming mechanism used by H. Pylori. H. Pylori is found to use a run-reverse swimming mechanism which I model as a random walk. This random walk model fits well to the experimental data and provides a theoretical tool for interpreting H. Pylori’s swimming mechanism. Taken together these results provide a detailed description of the motility of H. Pylori in different media and are applicable to the broad question of how H. pylori infects and colonizes the mucus layer of the stomach.

No description available.

Indiana University-Purdue University Indianapolis (IUPUI) / Cell shape changes and signaling pathways are essential for the development and function of the lens. During lens development proliferating epithelial cells will migrate down to the equator of the lens, differentiate into lens fiber cells, and begin to elongate along the lens capsule. The Fibroblast Growth Factor (FGF) signaling pathway has been extensively studied for its role in lens fiber cell differentiation and elongation. However, the main mediators of FGF stimulated lens fiber cell elongation have not been identified. Adaptor proteins Crk and CrkL are SH2- and SH3-containing proteins that transduce signals from upstream tyrosine phosphorylated proteins to downstream effectors, including Ras, Rac1 and Rap1, which are important for cell proliferation, adhesion and migration. Underlying their diverse function, these two adaptor proteins have been implicated in receptor tyrosine kinase signaling, focal adhesion assembly, and cell shape. To explore the role of Crk and CrkL in FGF signaling-dependent lens development and fiber elongation, we employed Cre/LoxP system to generate a lens specific knockout of Crk/CrkL. This led to extracellular matrix defects, disorganization of the lens fiber cells, and a defect in lens fiber cell elongation. Deletion of Crk and CrkL in the lens also mitigated the gain-of-function phenotype caused by overexpression of FGF3, indicating an epistatic relationship between Crk/CrkL and FGF signaling during lens fiber cell elongation. Further studies, revealed that the activity of Crk and CrkL in FGF signaling is controlled by the phosphatase Shp2 and the defect observed in lens fiber cell elongation can be rescued by constitutive activation of the GTPases Ras and Rac1 in the Crk and CrkL mutant lens. Interestingly, the deletion of the GTPases Rap1 in the lens showed no obvious phenotype pertaining to lens fiber cell elongation. These findings suggest that Crk and CrkL play an important role in integrating FGF signaling and mediating lens fiber cell elongation during lens development.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18502号 / 医博第3922号 / 新制||医||1005(附属図書館) / 31388 / 京都大学大学院医学研究科医学専攻 / (主査)教授 武藤 学, 教授 千葉 勉, 教授 松田 道行 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Dissertation (Ph.D.) -- University of Texas Southwestern Medical Center at Dallas, 2008. / Vita. Bibliography: p.116-124

The development and maintenance of tissues and organs depend on the careful regulation and coordinated motion of large numbers of cells. There is substantial evidence that many complex tissue functions, such as cell division, collective cell migration and gene expression, are directly regulated by mechanical forces. However, relatively little is known about how mechanical stress is distributed within a tissue and how this may guide biochemical signalling. Working in the framework of a popular vertex-based model, we derive expressions for stress tensors at the cell and tissue level to build analytic relationships between cell shape and mechanical stress. The discrete vertex model is upscaled, providing exact expressions for the bulk and shear moduli of disordered cellular networks, which bridges the gap to traditional continuum-level descriptions of tissues. Combining this theoretical work with new experimental techniques for whole-tissue stretching of Xenopus laevis tissue, we separate the roles of mechanical stress and cell shape in orienting and cueing epithelial mitosis. We find that the orientation of division is best predicted by the shape of tricellular junctions, while there appears to be a more direct role for mechanical stress as a mitotic cue.

No description available.