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.
authors.affiliation: Hematology Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Thon
authors.forename: Hannah
authors.initials: H
authors.lastname: Macleod
authors.forename: Antonija Jurak
authors.initials: AJ
authors.lastname: Begonja
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.forename: Kun-Chun
authors.initials: KC
authors.lastname: Lee
authors.forename: Alex
authors.initials: A
authors.lastname: Mogilner
authors.forename: John H
authors.initials: JH
authors.lastname: Hartwig
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Italiano
mesh_terms: D000199:Actins / Q000378:metabolism; D006801:Humans; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism*; D008962:Models, Theoretical; D009218:Myosins / Q000378:metabolism; D034061:Thrombopoiesis / Q000502:physiology
chemical_list: D000199:Actins; D009218:Myosins