New research from Rice University, Baylor College of Medicine (BCM) and the Puget Sound Blood Center (PSBC) has revealed how stresses of flow in the small blood vessels of the heart and brain could cause a common protein to change shape and form dangerous blood clots. The scientists were surprised to find that the proteins could remain in the dangerous, clot-initiating shape for up to five hours before returning to their normal, healthy shape.
The study -- the first of its kind -- focused on a protein called von Willebrand factor, or VWF, a key player in clot formation. A team led by Rice physicist Ching-Hwa Kiang found that "shear" forces, like those found in small arteries of patients with atherosclerosis, cause snippets of nonclotting VWF to change into a clot-forming shape for hours at a time. The finding appears online this week in Physical Review Letters.
"When I first heard what Dr. Kiang's team had found, I was shocked," said blood platelet expert Dr. Joel Moake, a study co-author who holds joint appointments at Rice and BCM. Moake, whose research group was the first to describe how high shear stress could cause platelets to stick to VWF, said, "I had thought that the condition might last for such a short time that it would be unmeasurable. No one expected to find that this condition would persist for hours. This has profound clinical implications."
Kiang, associate professor of physics and astronomy and of bioengineering, studies the forces involved in protein folding. Proteins are the workhorses of biology. Tens of thousands are produced each second in every living cell, and each of these folds into a characteristic shape within moments of its creation. Despite its ubiquity, protein folding is an immensely complex process that is shrouded in mystery.
Kiang is a pioneer in the use of atomic force microscopes (AFM) to shed light on the fundamental physical processes involved in protein folding. The AFM has a t
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