Characterization of the biomechanics of the GPIbα-vWF tether bond using von Willebrand Disease causing mutations R687E and wt vWF A1A2A3

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Title: Characterization of the biomechanics of the GPIbα-vWF tether bond using von Willebrand Disease causing mutations R687E and wt vWF A1A2A3
Author: Damaraju, Venkata Sitarama
Abstract: Platelet aggregation plays an important role in controlling bleeding by forming a hemostatic plug in response to vascular injuries. GPIbα is the platelet receptor that mediates the initial response to vascular injuries by tethering to the von Willebrand factor (vWF) on exposed subendothelium. When this occurs, platelets roll and then firmly adhere to the surface through the GPIIb-IIIa integrin present on the platelet surface. A hemostatic plug then forms by the aggregation of bound and free platelets which then seals the injury site. vWF is a multimer of many monomers, with each containing eleven domains. In this experiment, biomechanics of two of the eleven domains, gain of function (GOF) R687E vWF-A1 and wild type (wt) vWF-A1A2A3, were studied using videomicroscopy under varying shear stresses. This experiment used a parallel flow chamber coated along one surface with the vWF ligand. A solution containing platelets or Chinese Hamster Ovary (CHO) cells was perfused at varying shear stresses (0.5 dynes/cm2 to 512 dynes/ cm2) and cell-ligand interactions were recorded. Results showed that GOF R687E vWF exhibited slip bond behavior with increasing shear stress, whereas wt A1A2A3 vWF displayed a catch-slip bond transition with varying shear stresses. Interestingly, wt A1A2A3 vWF displayed two complete cycles of catch-slip bond behavior, which could be attributed to the structural complexity of the vWF ligand. However, more experiments need to be performed to further substantiate these claims. Information on the bonding behavior of each vWF can aid understanding of the biomechanics of the entire vWF molecule and associated diseases.
Description: The Tower is an official publication of the Georgia Tech Board of Student Publications and is sponsored by the Undergraduate Research Opportunities Program and the Price Gilbert Memorial Library System. This article is from Volume 2.
Type: Article
Date: 2010
Relation: The Tower. Volume 2.
Publisher: Georgia Institute of Technology
Subject: Circulating platelets
Vascular healing process
Advisor: Larry V. McIntire, School of Biomedical Engineering, Georgia Institute of Technology

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