Protein Mechanical Activation
Von Willebrand factor (VWF) is a large glycoprotein that is responsible for blood clotting and thrombosis. To maintain hemostasis, VWF mediates platelet adhesion to the subendothelial connective tissue that lines the interior of all blood vessels and binds to the clotting factor VIII. As a glycoprotein, it can reach up to 100 micrometers in length and can exhibit tremendous flexibility in its structure. VWF function is activated by an allosteric mechanism or by high-shear induced force. Beyond the allosteric model, VWF are generally regulated by hydrodynamic forces within the blood vessels. In blood vessels, the shear rate of fluid is at its maximum near the subendothelial wall. Shear-induced adhesion enables VWF to bind to the endothelial under pathophysiological conditions and to initiate the blood clotting process at the site of vessel damage. We are studying VWF and ultra-large VWF resistance to mechanical forces and the effect of shear induced property changes. We will also study the VWF properties in the presence of ADAMTS-13 to test its reductase activity.
DNA Melting and Phase Transition
The DNA-gold nanoparticle system is a model for phase transitions. Melting of short, free DNA is not a phase transition. However, when short DNA are bound to gold particles, the system undergoes a phase transition because the DNA-gold particles form networks of micrometer size, which is approaching a bulk phase. Thus, the binding transition in the network is much sharper than that of free DNA in solution, due to the cooperative melting process. Many fundamental aspects of phase transitions may be investigated with this biomolecular system.