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, Joseph E. Italiano

Research output: Contribution to journalArticle

86 Scopus citations

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.

Original languageEnglish (US)
Article number852
JournalNature Communications
Volume3
DOIs
StatePublished - 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

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    Thon, J. N., MacLeod, H., Begonja, A. J., Zhu, J., Lee, K. C., Mogilner, A., Hartwig, J. H., & Italiano, J. E. (2012). Microtubule and cortical forces determine platelet size during vascular platelet production. Nature Communications, 3, [852]. https://doi.org/10.1038/ncomms1838