Kiang, Ching-Hwa2013-07-242013-07-242013-07-242013-07-242012-122013-07-24December 2Wijeratne, 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>.https://hdl.handle.net/1911/71701The 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.application/pdfengCopyright 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.BiomoleculesProteinsSingle molecule manipulationAFM manipulation of a single moleculeVon Willebrand factorThesis2013-07-24123456789/ETD-2012-12-199