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dc.contributor.advisorBarker, Thomas H.
dc.contributor.authorFiore, Vincent F.
dc.date.accessioned2016-05-27T13:05:21Z
dc.date.available2016-05-27T13:05:21Z
dc.date.created2014-05
dc.date.issued2014-04-07
dc.date.submittedMay 2014
dc.identifier.urihttp://hdl.handle.net/1853/54835
dc.description.abstractFibrosis of vital organs remains one of the leading causes of death in the developed world, where it occurs predominantly in soft tissues (liver, lung, kidney, heart) through fibroblast proliferation and deposition of extracellular matrix (ECM). In the process of fibrosis, remodeling and deposition of ECM results in stiffening of cellular microenvironment; cells also respond to these changes in the stiffness through engagement of their cytoskeleton and signaling via cell-ECM contacts. Thus, understanding to what extent the stiffness of the cellular microenvironment changes as a consequence of fibrotic progression, and how cells respond to this change, is critical. In this thesis, we quantitatively measured stiffness of the lung parenchyma and its changes during fibrosis. We find that the average stiffness increases by approximately 10-fold. We then investigated how changes in ECM rigidity affect the cytoskeletal phenotype of lung fibroblasts. We find a complex relation between expression of the glycoprotein Thy-1 (CD90) and ECM rigidity-dependent cytoskeletal phenotype (i.e. “mechanotransduction”). Finally, we investigate a mechanism for the regulation of rigidity sensing by Thy-1 and its involvement in intracellular signaling through cell-ECM contacts. Taken together, this work helps define in vivo parameters critical to the fibrogenesis program and to define unique cellular phenotypes that may respond or contribute to mechanical homeostasis in fibrotic diseases.
dc.format.mimetypeapplication/pdf
dc.language.isoen_US
dc.publisherGeorgia Institute of Technology
dc.subjectFibrosis
dc.subjectFibroblast
dc.subjectExtracellular matrix
dc.subjectMechanotransduction
dc.subjectMicroenvironment
dc.subjectPulmonary
dc.subjectTissue mechanics
dc.subjectWound healing
dc.titleInvestigation of mechanotransductory mechanisms in the pathogenesis of lung fibrosis
dc.typeDissertation
dc.description.degreePh.D.
dc.contributor.departmentBiomedical Engineering (Joint GT/Emory Department)
thesis.degree.levelDoctoral
dc.contributor.committeeMemberGarcía, Andrés J.
dc.contributor.committeeMemberHagood, James S.
dc.contributor.committeeMemberSantangelo, Philip
dc.contributor.committeeMemberZhu, Cheng
dc.date.updated2016-05-27T13:05:21Z


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