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Investigation of the Biochemical Mechanism for Cell-Substrate Mechanical Sensing

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dc.contributor.advisor Rafailovich, Miriam en_US
dc.contributor.advisor Simon, Marcia en_US
dc.contributor.author Ricotta, Vincent Anthony en_US
dc.contributor.other Department of Materials Science and Engineering. en_US
dc.date.accessioned 2017-09-20T16:50:04Z
dc.date.available 2017-09-20T16:50:04Z
dc.date.issued 2014-12-01 en_US
dc.identifier.uri http://hdl.handle.net/11401/76343 en_US
dc.description 53 pg. en_US
dc.description.abstract Advancements in stem cell biology and materials science have enabled the development of new treatments for tissue repair. Dental pulp stem cells (DPSCs), which are highly proliferative and can be induced to differentiate along several mesenchymal cell lineages, offer the possibility for pulpal regeneration and treatment of injured dentition. Polybutadiene (PB) may be used as a substrate for these cells. This elastomer can be spun casted into films of different thicknesses with different moduli. DPSCs grown on PB films, which are relatively hard (less than 1500 Ã… thick), biomineralize depositing crystalline calcium phosphate without a requirement for the typical induction factor, dexamethasone (Dex). The moduli of cells track with the moduli of the surface suggesting that mechanics controls mineralization. The purpose of this study was to determine whether the major effect of Dex on biomineralization is the result of its ability to alter cell mechanics or its ability to induce osteogenesis/odontogenesis. DPSCs sense substrate mechanics through the focal adhesions, whose function is in part regulated by the Ras homolog gene (Rho) and its downstream effectors Rho associated kinases (ROCKs). ROCKs control actin filament polymerization and interactions with myosin light chain. Because cells sense substrate mechanics through focal adhesion proteins whose function is regulated by ROCKs, the impact of a ROCK inhibitor, Y-27632, was monitored. Blocking this pathway with Y-27632 suppressed the ability of DPSCs to sense the PB substrate. The cell modulus, plasma membrane stiffness, and cytosol stiffness were all lowered and biomineralization was suppressed in all cultures independent of substrate modulus or the presence of Dex. In other words, the inability of DPSCs to sense mechanical cues suppressed their ability to promote mineralization. On the other hand the expression of osteogenic/odontogenic markers (alkaline phosphatase and osteocalcin) was enhanced, perhaps due to Y-27632 induced changes in Wnt signaling as seen in other mesenchymal stem cells. How mechanical sensing regulates matrix proteins to promote their mineralization remains an open question. en_US
dc.description.sponsorship This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. en_US
dc.format Monograph en_US
dc.format.medium Electronic Resource en_US
dc.language.iso en_US en_US
dc.publisher The Graduate School, Stony Brook University: Stony Brook, NY. en_US
dc.subject.lcsh Materials Science en_US
dc.subject.other Dex, DPSC, Mineralization, Polybutadiene, Y-27632 en_US
dc.title Investigation of the Biochemical Mechanism for Cell-Substrate Mechanical Sensing en_US
dc.type Thesis en_US
dc.mimetype Application/PDF en_US
dc.contributor.committeemember Sokolov, Jonathon. en_US

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