Force Activation of a Multimeric Adhesive Protein through Domain Conformational Change

dc.contributor.advisorKiang, Ching-Hwa
dc.contributor.committeeMemberTao, Yizhi Jane
dc.contributor.committeeMemberKono, Junichiro
dc.creatorWijeratne, Sitara
dc.date.accessioned2013-07-24T19:50:30Z
dc.date.accessioned2013-07-24T19:50:33Z
dc.date.available2013-07-24T19:50:30Z
dc.date.available2013-07-24T19:50:33Z
dc.date.created2012-12
dc.date.issued2013-07-24
dc.date.submittedDecember 2012
dc.date.updated2013-07-24T19:50:33Z
dc.description.abstractThe force-induced activation of adhesive proteins such as von Willebrand Factor (VWF), which experience high hydrodynamic forces, is essential in initiating platelet adhesion. The importance of the mechanical force induced functional change is manifested in the multimeric VWF’s crucial role in blood coagulation, when high fluid shear stress activates pVWF multimers to bind platelets. Here we showed that a pathological level of high shear flow exposure of pVWF multimers results in domain conformational changes, and the subsequent shifts in the unfolding force allow us to use force as a marker to track the dynamic states of multimeric VWF. We found that shear-activated pVWF multimers (spVWF) are more resistant to mechanical unfolding than non-sheared pVWF multimers, as indicated in the higher peak unfolding force. These results provide insight into the mechanism of shear-induced activation of pVWF multimers.
dc.format.mimetypeapplication/pdf
dc.identifier.citationWijeratne, Sitara. "Force Activation of a Multimeric Adhesive Protein through Domain Conformational Change." (2013) Master’s Thesis, Rice University. <a href="https://hdl.handle.net/1911/71701">https://hdl.handle.net/1911/71701</a>.
dc.identifier.slug123456789/ETD-2012-12-199
dc.identifier.urihttps://hdl.handle.net/1911/71701
dc.language.isoeng
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.
dc.subjectBiomolecules
dc.subjectProteins
dc.subjectSingle molecule manipulation
dc.subjectAFM manipulation of a single molecule
dc.subjectVon Willebrand factor
dc.titleForce Activation of a Multimeric Adhesive Protein through Domain Conformational Change
dc.typeThesis
dc.type.materialText
thesis.degree.departmentApplied Physics
thesis.degree.disciplineNatural Sciences
thesis.degree.grantorRice University
thesis.degree.levelMasters
thesis.degree.nameMaster of Science
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