Microtubule and cortical forces determine platelet size during vascular platelet production

Jonathan N Thon, Hannah Macleod, Antonija Jurak Begonja, Jie Zhu, Kun-Chun Lee, Alex Mogilner, John H. Hartwig and Joseph E. Italiano ()
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Jonathan N Thon: Brigham and Women's Hospital
Hannah Macleod: Brigham and Women's Hospital
Antonija Jurak Begonja: Harvard Medical School
Jie Zhu: University of California Davis
Kun-Chun Lee: University of California Davis
Alex Mogilner: University of California Davis
John H. Hartwig: Harvard Medical School
Joseph E. Italiano: Brigham and Women's Hospital

Nature Communications, 2012, vol. 3, issue 1, 1-9

Abstract: Abstract Megakaryocytes release large preplatelet intermediates into the sinusoidal blood vessels. Preplatelets convert into barbell-shaped proplatelets in vitro to undergo repeated abscissions that yield circulating platelets. These observations predict the presence of circular-preplatelets and barbell-proplatelets in blood, and two fundamental questions in platelet biology are what are the forces that determine barbell-proplatelet formation, and how is the final platelet size established. Here we provide insights into the terminal mechanisms of platelet production. We quantify circular-preplatelets and barbell-proplatelets in human blood in high-resolution fluorescence images, using a laser scanning cytometry assay. We demonstrate that force constraints resulting from cortical microtubule band diameter and thickness determine barbell-proplatelet formation. Finally, we provide a mathematical model for the preplatelet to barbell conversion. We conclude that platelet size is limited by microtubule bundling, elastic bending, and actin-myosin-spectrin cortex forces.

Date: 2012
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DOI: 10.1038/ncomms1838

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