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Microtubule and cortical forces determine platelet size during vascular platelet production

Author

Listed:
  • Jonathan N Thon

    (Brigham and Women's Hospital
    Harvard Medical School)

  • Hannah Macleod

    (Brigham and Women's Hospital)

  • Antonija Jurak Begonja

    (Harvard Medical School
    Brigham and Women's Hospital)

  • 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
    Brigham and Women's Hospital)

  • Joseph E. Italiano

    (Brigham and Women's Hospital
    Harvard Medical School
    Vascular Biology Program, Children's Hospital)

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.

Suggested Citation

  • Jonathan N Thon & Hannah Macleod & Antonija Jurak Begonja & Jie Zhu & Kun-Chun Lee & Alex Mogilner & John H. Hartwig & Joseph E. Italiano, 2012. "Microtubule and cortical forces determine platelet size during vascular platelet production," Nature Communications, Nature, vol. 3(1), pages 1-9, January.
    • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms1838
    DOI: 10.1038/ncomms1838
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    Cited by:

    1. Christopher Cyrus Kuhn & Nirakar Basnet & Satish Bodakuntla & Pelayo Alvarez-Brecht & Scott Nichols & Antonio Martinez-Sanchez & Lorenzo Agostini & Young-Min Soh & Junichi Takagi & Christian Biertümpf, 2023. "Direct Cryo-ET observation of platelet deformation induced by SARS-CoV-2 spike protein," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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