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

75 Citations (Scopus)

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

Fingerprint

Platelets
platelets
Microtubules
Blood Vessels
Blood Platelets
blood
Blood
Laser Scanning Cytometry
elastic bending
myosins
Spectrin
Megakaryocytes
cytometry
cortexes
blood vessels
Blood vessels
Myosins
biology
Actins
Assays

ASJC Scopus subject areas

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

Cite this

Thon, J. N., MacLeod, H., Begonja, A. J., Zhu, J., Lee, K. C., Mogilner, A., ... 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

Microtubule and cortical forces determine platelet size during vascular platelet production. / Thon, Jonathan N.; MacLeod, Hannah; Begonja, Antonija Jurak; Zhu, Jie; Lee, Kun Chun; Mogilner, Alex; Hartwig, John H.; Italiano, Joseph E.

In: Nature Communications, Vol. 3, 852, 2012.

Research output: Contribution to journalArticle

Thon, JN, MacLeod, H, Begonja, AJ, Zhu, J, Lee, KC, Mogilner, A, Hartwig, JH & Italiano, JE 2012, 'Microtubule and cortical forces determine platelet size during vascular platelet production', Nature Communications, vol. 3, 852. https://doi.org/10.1038/ncomms1838
Thon, Jonathan N. ; MacLeod, Hannah ; Begonja, Antonija Jurak ; Zhu, Jie ; Lee, Kun Chun ; Mogilner, Alex ; Hartwig, John H. ; Italiano, Joseph E. / Microtubule and cortical forces determine platelet size during vascular platelet production. In: Nature Communications. 2012 ; Vol. 3.
@article{51af54d9096b402b99a07030ee51b2fe,
title = "Microtubule and cortical forces determine platelet size during vascular platelet production",
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.",
author = "Thon, {Jonathan N.} and Hannah MacLeod and Begonja, {Antonija Jurak} and Jie Zhu and Lee, {Kun Chun} and Alex Mogilner and Hartwig, {John H.} and Italiano, {Joseph E.}",
year = "2012",
doi = "10.1038/ncomms1838",
language = "English (US)",
volume = "3",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Microtubule and cortical forces determine platelet size during vascular platelet production

AU - Thon, Jonathan N.

AU - MacLeod, Hannah

AU - Begonja, Antonija Jurak

AU - Zhu, Jie

AU - Lee, Kun Chun

AU - Mogilner, Alex

AU - Hartwig, John H.

AU - Italiano, Joseph E.

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84865430590&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84865430590&partnerID=8YFLogxK

U2 - 10.1038/ncomms1838

DO - 10.1038/ncomms1838

M3 - Article

VL - 3

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 852

ER -