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dc.contributor.advisorHumphrey, Jay Den_US
dc.creatorNa, Sungsooen_US
dc.date.accessioned2010-01-15T00:16:14Zen_US
dc.date.accessioned2010-01-16T02:03:44Z
dc.date.available2010-01-15T00:16:14Zen_US
dc.date.available2010-01-16T02:03:44Z
dc.date.created2006-05en_US
dc.date.issued2009-06-02en_US
dc.identifier.urihttp://hdl.handle.net/1969.1/ETD-TAMU-1704
dc.description.abstractThe cytoskeleton is a diverse, multi-protein framework that plays a fundamental role in many cellular activities including mitosis, cell division, intracellular transport, cell motility, muscle contraction, and the regulation of cell polarity and organization. Furthermore, cytoskeletal filaments have been implicated in the pathogenesis of a wide variety of diseases including cancer, blood disease, cardiovascular disease, inflammatory disease, neurodegenerative disease, and problems with skin, nail, cornea, hair, liver and colon. Increasing evidence suggests that the distribution and organization of the cytoskeleton in living cells are affected by mechanical stresses and the cytoskeleton determines cell stiffness. We developed a fully nonlinear, constrained mixture model for adherent cells that allows one to account separately for the contributions of the primary structural constituents of the cytoskeleton and extended a prior solution from the finite elasticity literature for use in a sub-class of atomic force microscopy (AFM) studies of cell mechanics. The model showed that the degree of substrate stretch and the geometry of the AFM tip dramatically affect the measured cell stiffness. Consistent with previous studies, the model showed that disruption of the actin filaments can reduce the stiffness substantially, whereas there can be little contribution to the overall cell stiffness by the microtubules or intermediate filaments. To investigate the effect of mechanical stretching on cytoskeletal remodeling and cell stiffness, we developed a simple cell-stretching device that can be combined with an AFM and confocal microscopy. Results demonstrate that cyclic stretching significantly and rapidly alters both cell stiffness and focal adhesion associated vinculin and paxillin, suggesting that focal adhesion remodeling plays a critical role in cell stiffness by recruiting and anchoring F-actin. Finally, we estimated cytoskeletal remodeling by synthesizing data on stretch-induced dynamic changes in cell stiffness and focal adhesion area using constrained mixture approach. Results suggest that the acute increase in stiffness in response to an increased cyclic stretch was probably due to an increased stretch of the original filaments whereas the subsequent decrease back towards normalcy was consistent with a replacement of the highly stretched original filaments with less stretched new filaments.en_US
dc.format.mediumelectronicen_US
dc.format.mimetypeapplication/pdfen_US
dc.language.isoen_USen_US
dc.subjectconstrained mixture modelen_US
dc.subjectatomic force microscopyen_US
dc.subjectfluorescent labelingen_US
dc.subjectfocal adhesionsen_US
dc.subjectcyclic stretchen_US
dc.titleEffects of mechanical forces on cytoskeletal remodeling and stiffness of cultured smooth muscle cellsen_US
dc.typeBooken
dc.typeThesisen
thesis.degree.departmentBiomedical Engineeringen_US
thesis.degree.disciplineBiomedical Engineeringen_US
thesis.degree.grantorTexas A&M Universityen_US
thesis.degree.nameDoctor of Philosophyen_US
thesis.degree.levelDoctoralen_US
dc.contributor.committeeMemberCriscione, John Cen_US
dc.contributor.committeeMemberHwang, Wonmuken_US
dc.contributor.committeeMemberMeininger, Gerald Aen_US
dc.contributor.committeeMemberWu, Hsin-ien_US
dc.type.genreElectronic Dissertationen_US
dc.type.materialtexten_US
dc.format.digitalOriginborn digitalen_US


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