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Stressed proteins can cause blood clots for hours
Date:3/5/2013

iny needle with a tip measuring just a few atoms across. The needle is suspended from a tiny arm that bobs up and down over a surface. Kiang's team uses the bobbing needle to grab and pull apart individual protein molecules. By stretching these like rubber bands, her team has shown it can measure the precise physical forces that hold them in their folded shape.

"In this study, we did more than just measure the forces; we used those measurements to see what state the molecule was in," Kiang said. "In this way, we were able to study the dynamics of the molecule, to see how it changed over a period of time."

Moake, a senior research scientist in bioengineering at Rice and professor of medicine at BCM, said the work is vitally important because it helps explain the workings of VWF.

"VWF is synthesized in the cells that line the walls of blood vessels, and it's stored there until the cells get signals that the vessels are in danger of injury," Moake said. "In response to those stimuli, the cell secretes VWF. It's a long protein, and one end remains anchored to the cell while the rest unfurls from the wall like a streamer."

The act of unfurling makes VWF sticky for platelets, and that begins the process of hemostasis, which prevents people from bleeding to death when blood vessels are damaged by cuts and wounds.

"The body recognizes when clotting must stop -- when there are too many strings, too much sticking, too many platelet clumps -- and it uses an enzyme to clip the long VWF strings," Moake explained. "First, it makes large, soluble versions of the strings that remain somewhat sticky, and then these large soluble portions of VWF are reduced into smaller subunits of VWF that circulate in the plasma."

Under normal conditions, these circulating subunits, which are called PVWF, fold into compact shapes and cease to be sticky to platelets. However, previous research had shown that a type of physical stress called "shea
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Contact: David Ruth
david@rice.edu
713-348-6327
Rice University
Source:Eurekalert

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