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Anticoagulation
Laser Tweezers Help Doctors Understand Blood Clots
Using "laser tweezers," researchers at the University of Pennsylvania School of Medicine have measured the strength of the bond between a single integrin molecule on the surface of a platelet and a molecule of fibrinogen, a clotting protein found in the bloodstream.
These findings refine the current paradigm of how blood clots form. They show that changes in an integrin's ability to bind to fibrinogen are regulated by the cell as an all-or-none phenomenon with only one functional state compatible with binding. The researchers also offer a new application for laser tweezers in studying the behavior of single molecules and the response of cells to mechanical forces.
Clotting is the body's first defense against damage to blood vessels. When damaged, the cells that make up blood vessels release chemicals that activate passing platelets, causing them to adhere to the surface and aggregate. While clotting may stop bleeding, the formation of thrombi, or blood clots where they do not belong, may also lead to a stroke or heart attack if a clot blocks off blood vessels. So the subject of the forces involved in how clots form and dissolve are important to medical researchers. The regulation of activation of these cellular integrins must be tightly controlled to prevent thrombosis.
The trick to uncovering the strength of a single bond between proteins was the use of the laser tweezers. Laser tweezers cannot manipulate individual molecules, as such, but Penn scientists developed a new model system using tiny pedestals and beads that can be trapped and moved. To measure the bond strength, the researchers actually attached fibrinogen to microscopic plastic beads and exposed them to integrin that was either attached to pedestals or as they sat on the surface of living, reactive platelet cells.
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