UC Davis mathematicians have helped biologists figure out why platelets, the cells that form blood clots, are the size and shape that they are. Because platelets are important both for healing wounds and in strokes and other conditions, a better understanding of how they form and behave could have wide implications.
"Platelet size has to be very specific for blood clotting," said Alex Mogilner, professor of mathematics, and neurobiology, physiology and behavior at UC Davis and a co-author of the paper, published this week in the journal Nature Communications. "It's a longstanding puzzle in platelet formation, and this is the first quantitative solution."
Mogilner and UC Davis postdoctoral scholars Jie Zhu and Kun-Chun Lee developed a mathematical model of the forces inside the cells that turn into platelets, accurately predicting their final size and shape.
They were collaborating with a team led by Joseph Italiano and Jonathon Thon at Harvard Medical School and Brigham and Women's Hospital, Boston.
Platelets are made by bone marrow cells called megakaryocytes. They bud off first as large, circular pre-platelets, form into a dumbbell-shaped pro-platelet, then finally divide into a standard-sized, disc-shaped platelet. A typical person has about a trillion platelets in circulation at a time, and makes about 100 billion new platelets a day, each living for 8 to 10 days.
Inside the pre- and pro-platelets is a ring of protein microtubules, which exerts pressure to straighten and broaden the nascent cells. But overlying the ring is a rigid cortex of proteins that prevents the platelets from expanding.
By tweaking the number of microtubules in the bundles, Mogilner, Zhu and Lee found that they could correctly predict how pro-platelets would flip into a dumbbell shape, as well as the size and shape of mature platelets.
The work grew out of a long-standing collaboration between Mogilner and the Harvard team -- the kind of cross-disciplinary research that makes UC Davis a center for innovation. It was supported by the National Institutes of Health and the National Science Foundation.
- Jonathan N Thon, Hannah Macleod, Antonija Jurak Begonja, Jie Zhu, Kun-Chun Lee, Alex Mogilner, John H. Hartwig, Joseph E. Italiano. Microtubule and cortical forces determine platelet size during vascular platelet production. Nature Communications, 2012; 3: 852 DOI: 10.1038/ncomms1838
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