On the transmission of fluid forces to the actin cytoskeleton of bone and endothelial cells.
Item
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Title
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On the transmission of fluid forces to the actin cytoskeleton of bone and endothelial cells.
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Identifier
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AAI3205454
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identifier
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3205454
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Creator
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Han, Yuefeng.
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Contributor
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Advisers: Sheldon Weinbaum | Stephen C. Cowin | Mitchell B. Schaffler
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Date
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2006
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Language
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English
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Publisher
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City University of New York.
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Subject
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Engineering, Biomedical | Biophysics, Medical | Biophysics, General
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Abstract
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This dissertation studies how hydrodynamic forces are transmitted across the membranes of endothelial cells and bone cells (osteocytes) via extracellular matrices. Firstly, I apply large deformation theory for 'elastica' to describe the restoration of the core protein fibers in the endothelial glycocalyx (EG) after being matted by the passage of a white blood cell. By matching the predicted time-dependent thickness of the EG with experiments I obtain an estimate of 490 pN·nm2 for the flexural rigidity of the core protein fibers. Thus, the EG is sufficiently stiff to function as a mechanotransducer. The core proteins are also barely deflected by the physiological motion of red blood cells (RBCs). In contrast, arrested RBCs crush the EG and the viscous draining resistance of the EG layer is essential for preventing adhesive intercellular interactions between endothelial cells and RBCs. Secondly, I model the response of the EG to steady or oscillating shear applied at its edge, and extend this analysis to apply to the microvilli and cilia on kidney cells. In the case of oscillating shear, I find that the motions of both the fluid and structural elements, including the EG and microvilli and cilia on kidney cells, are in a quasi-steady state at physiological conditions. Thirdly, I develop a realistic 3-D structural model for the core actin bundle in osteocytic processes, and greatly refine the strain amplification model for bone mechanotransduction proposed by You et al. (2001, J. Biomech. 34: 1375). The new model predicts a cell process that is 3 times stiffer than You et al. (2001), but hoop strains > 0.5 percent for tissue level strains > 1000 mu strain at 1 Hz and > 250 mu strain at frequencies > 10 Hz. This strain amplification model provides a more likely hypothesis for the excitation of osteocytes than the fluid shear hypothesis previously proposed in Weinbaum et al. (1994, J. Biomech. 27: 339). Finally, I study the fluorescence uptake by osteocyte-like MLO-Y4 cells incubated with agonists and antagonists to purinergic P2X7 receptors. The results suggest the involvement of P2X 7 receptors in the signaling pathway for the mechanotransduction of osteocytes.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
