Platelets are cells in the blood whose job is to stop bleeding by sticking together to form clots and plug up a wound. Now, for the first time, scientists have measured and mapped the key molecular forces on platelets that trigger this process.
The extensive results are published in two separate studies, in the Proceedings of the National Academy of Sciences (PNAS) and in Nature Methods. “We show conclusively that, in order to activate clotting, the cell needs a targeted force of a magnitude of just a few piconewtons — or a force about a billion times less than the weight of a staple,” says Khalid Salaita, associate professor in Emory University’s Department of Chemistry and the lead author of the studies. “The real surprise we found is that platelets care about the direction of that force and that it has to be lateral. They’re very picky. But they should be picky because otherwise they might accidentally create a clot. That’s what causes strokes.”
Fibrinogen, the third most abundant protein in blood, acts like glue to stick platelets together as a clot forms. Each platelet has about 70,000 copies of a receptor for fibrinogen on its surface. These receptors can work like grappling hooks to latch onto fibrinogen.
“What was puzzling,” Salaita explains, “is that platelets, despite having all these receptors, do not normally latch onto the abundant fibrinogen. They keep flowing past it until you have an injury and fibrinogen becomes anchored. Then the platelets rapidly bind to fibrinogen allowing platelets to aggregate and for clotting to proceed.”
The Salaita lab is a leader in visualizing and mapping the mechanical forces applied by cells. In order to explore the biomechanics of blood clotting, the lab teamed up with physician and biomedical engineer Wilbur Lam, an expert in hematology at Emory’s School of Medicine. Both Salaita and Lam are also affiliated with Emory’s Winship Cancer Institute and the Wallace H. Coulter Department of Biomedical Engineering at Emory and Georgia Tech.
An electron micrograph shows a red blood cell, an activated platelet (in yellow) and a white blood cell. The ability to map the magnitude and orientation of forces on a cell provides a new tool for investigating not just blood clotting but a range of biomechanical processes. (NCI photo)