Unformatted text preview: Platelet Accumulation when shear rate > 1000 s-1 Thrombosis to occlusion occurs in
< 30 min • • Biophysics at the nanoscale nanoscale Implications: Surface and Bonding Implications:
o Collagen Surface?
1000 plts adhere to surface 1 billion aggregate to occlusion o Aggregation is super fast
Capture time <10 microseconds Compare to previous reports of Compare GPIb-vWF bond kinetics Alon/Springer (1997)– “…L-selectin is “… faster than any known adhesion molecule” Miura (2000) static – 10 min Miura Doggett (2003) low shear - 7/s Kumar (2003) med shear – 7/s Kumar Arya (2005) optical tweezers ~ 0.02 s Now ~ 10 microsecond! Bond Force Bond F = 2 x shear x viscosity x area = shear x 10-3 x 10 x 10-12 Usual shear of 1000 s-1 gives 10 pN Here shear can reach 200,000 s-1 so Here Bond Force / platelet ~ 2,000 pN
(Mody/King 05) (Yago/Zhu 06) Bonding different in disease Bonding
Bonding is 10,000x faster than previously reported Bonding is 20x stronger than previously reported for GPIb integrin bond No activation of circulating platelets New adhesion molecules or mechanism? Kumar Biophys J 2003 QuickTime™ and a decompressor are needed to see this picture. Gibbins, JCS 2004 Multivalent Bonding Multivalent
Shear Rate (s-1) Force (pN) 10,000 1,700 50,000 8,500 100,000 17,000 500,000 85,000 Bonds 17 85 170 850 vWF: Globular to Strand for vWF shear >5000 s-1 vWF: shape matters vWF Activation release more vWF vWF over time More bonds at high shear More Only sticky when needed Summary Platelets are needed for hemostasis Problem is when it causes a heart attack or stroke Biophysics shows that body does some amazing things: Captures platelets...
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- Fall '10
- Atherosclerosis, vWF, low shear vWF