Unformatted text preview: only at very high velocity and shear Summary High bond strength by progressive bonding:
• Elongate vWF • Release more vWF • Net of strands with bonds matching plt • Like Velcro hooks and loops Captures in less than 10 microseconds How to stop a Heart How Attack?
Stop platelets at high shear by blocking: nfolding of vWF U Unfolding vWF Release of vWF Release vWF Network conformation Conclusion Conclusion Basic physics of blood clotting can lead to new therapies to prevent heart attacks and strokes without the side effects of bleeding Thrombosis Thrombosis in Diseased Arteries David N Ku, MD, PhD Possible Mechanisms Multivalent Bonding Sulchek PNAS 05 Unfolding of vWF Schneider PNAS 06 Activation of mural platelets for vWF Rate limiting step may be convection of platelets to the surface Thrombosis at high shear Thrombosis
I. Platelets adhere to collagen surface
• Circulating vWF + GPIb II. Platelets aggregate to thrombus
• vWF released from mural platelets • vWF elongates to expose A1’s • Growth rate dependent on platelet arrival Conclusions Arterial thrombosis requires v high shear >1000 s-1 Bond kinetics super fast <10 µsec Bond strength from multivalency? Prevent occlusion by altering:
• Convection of platelets • vWF unfolding • Without affecting bleeding time...
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- Fall '10
- Atherosclerosis, vWF, low shear vWF