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

doi:10.1038/ncomms1838

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 journal › Article › peer-review

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 language	English (US)
Article number	852
Journal	Nature communications
Volume	3
DOIs	https://doi.org/10.1038/ncomms1838
State	Published - 2012

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

Access to Document

10.1038/ncomms1838

Cite this

@article{cd32436c598c4501a8fae71dcb884c0d,

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.}",

note = "Funding Information: This work was supported in part by the National Institutes of Health grant Hl68130 (J.E.I.) and NSF grant DMS-1118206 (A.M.). J.E.I. is an American Society of Hematology Junior Faculty Scholar. J.N.T. is an American Society of Hematology Scholar. We acknowledge the staff at CompuCyte for access to their laser scanning cytometer and support in building the analysis modules described in this manuscript; and Dr. Herv{\'e} Falet at Harvard Medical School for access to his Filamin A KO mice.",

year = "2012",

doi = "10.1038/ncomms1838",

language = "English (US)",

volume = "3",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Research",

}

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.

N1 - Funding Information: This work was supported in part by the National Institutes of Health grant Hl68130 (J.E.I.) and NSF grant DMS-1118206 (A.M.). J.E.I. is an American Society of Hematology Junior Faculty Scholar. J.N.T. is an American Society of Hematology Scholar. We acknowledge the staff at CompuCyte for access to their laser scanning cytometer and support in building the analysis modules described in this manuscript; and Dr. Hervé Falet at Harvard Medical School for access to his Filamin A KO mice.

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

C2 - 22617292

AN - SCOPUS:84865430590

SN - 2041-1723

VL - 3

JO - Nature communications

JF - Nature communications

M1 - 852

ER -

Microtubule and cortical forces determine platelet size during vascular platelet production

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this