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Exploring the molecular origin of blood clot flexibility

t the molecular level, it may eventually be possible to see how they relate to the mechanical properties of single fibers and a whole clot. This knowledge may enable researchers to make predictions about the function of differently formed fibrin clots in the circulating blood or in a wound. For example, when clots are not stiff enough, problems with bleeding arise, and when clots are too stiff, there may be problems with thrombosis, which results when clots block the flow of blood. First author André Brown, a physics graduate student at Penn, notes that this research is a first step towards understanding the mechanics of the relationship between clot elasticity and disease.

Recent research by other scientists showed that a fibrin fiber could stretch four to five times its original length before snapping. "This is among the most extensible, or stretchy, of polymers that anyone has ever found," says Weisel. "But, how is the stretching happening at a molecular level? We think part of it has to be the unfolding of certain parts of the fibrin molecule, otherwise how can it stretch so much?"

Previous research from senior coauthor Dennis Discher, PhD, Professor in the Physics and Cell & Molecular Biology graduate groups, suggested the possibility that alpha-helical structures in some blood-cell proteins unfold at low levels of mechanical force. But "it wasn't known before that the coiled coil region of the fibrinogen molecule would be the part to unfold under the stress induced by the atomic force microscope," notes Brown.

Once the origins of the mechanical properties of clots are well understood, it may be possible to modulate those properties, note the study authors. "If we can change a certain parameter perhaps we can make a clot that's more or less stiff," explains Weisel. For example, various peptides or proteins, such as antibodies, bind specifically to fibrin, affecting clot structure. The idea would be to use such compounds in peo
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Source:University of Pennsylvania School of Medicine


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