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Exploring the molecular origin of blood clot flexibility

(PHILADELPHIA) How do blood clots maintain that precise balance of stiffness for wound healing and flexibility to go with the flow? Researchers at the University of Pennsylvania School of Medicine and the School of Arts and Sciences have shown that a well-known protein structure acts as a molecular spring, explaining one way that clots may stretch and bend under such physical stresses as blood flow. They report their findings in a Letter in the latest online edition of the Biophysical Journal. This knowledge will inform researchers about clot physiology in such conditions as wound healing, stroke, and cardiovascular disease.

Clots are a three-dimensional network of fibers, made up primarily of the blood protein fibrinogen, which is converted to fibrin during clotting. A blood clot needs to have the right degree of stiffness and plasticity to stem the flow of blood when tissue is damaged, yet be flexible enough so that it does not block blood flow and cause heart attacks and strokes.

In previous research, senior author John W. Weisel, PhD, Professor of Cell and Developmental Biology, measured the elastic properties of individual fibers and found that the fibers, which are long and very thin, bend much more easily than they stretch, suggesting that clots deform in flowing blood or under other stresses, primarily by the bending of their fibers.

The current research extends those earlier findings to the molecular level, suggesting a way that individual fibers flex - by the unraveling of the three, tightly twisted rod-like regions within fibrinogen molecules, called alpha-helical coiled-coils. The researchers measured this change by pulling engineered strands of fibrinogen molecules using an atomic force microscope. This alpha-helical coiled-coil "spring" is a common motif in protein structure, first identified more than 50 years ago and so its stretchiness may have broader implications in biology and medicine.

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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
12-Jan-2007


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