Ciciliano Jordan C, Tran Reginald, Sakurai Yumiko, Lam Wilbur A
Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA; Parker H. Petit Institute of Bioengineering & Bioscience, Georgia Institute of Technology, Atlanta, GA, USA; Winship Cancer Institute of Emory University, Atlanta, GA, USA.
Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA; Winship Cancer Institute of Emory University, Atlanta, GA, USA.
Thromb Res. 2014 Apr;133(4):532-7. doi: 10.1016/j.thromres.2013.12.037. Epub 2014 Jan 4.
While the role of platelets in hemostasis is well characterized from a biological perspective, the biophysical interactions between platelets and their mechanical microenvironment are relatively unstudied. The field of cellular mechanics has developed a number of approaches to study the effects of extracellular matrix (ECM)-derived mechanical forces on various cells, and has elucidated that integrin-cytoskeleton-mediated force transduction governs many cellular processes. As platelets adhere and spread via molecular machinery that is similar to that which enables other cells to mechanosense and mechanotransduce forces from their biophysical microenvironment, platelets too are likely governed by the same overarching mechanisms. Indeed, recent platelet mechanobiology studies have revealed that key aspects of platelet physiology and activation are regulated by the mechanical and spatial properties of the ECM microenvironment. At the same time, there are also key differences that make platelets unique in the world of cells-- their size, origin as megakaryocyte fragments, and unique αIIbβ3 integrin-- render their mechanosensing activities particularly interesting. The structurally "simple," anucleate nature of platelets coupled with their high actin concentration (20% of total protein) and integrin density [1] seem to make them ideal for mechanical force generation and transmission. Further studies will enhance our understanding of the role of platelet mechanobiology in hemostasis and thrombosis, potentially leading to new categories of diagnostics that investigate the mechanical properties of clots to determine bleeding risk, as well as therapies that target the mechanotransduction signaling pathway to alter the stability of clots.
虽然从生物学角度来看，血小板在止血过程中的作用已得到充分表征，但血小板与其机械微环境之间的生物物理相互作用相对较少被研究。细胞力学领域已经开发出多种方法来研究细胞外基质（ECM）衍生的机械力对各种细胞的影响，并阐明整合素-细胞骨架介导的力转导控制着许多细胞过程。由于血小板通过与使其他细胞能够感知和转导来自其生物物理微环境的力的分子机制相似的方式黏附并铺展，血小板很可能也受相同的总体机制支配。事实上，最近的血小板机械生物学研究表明，血小板生理学和激活的关键方面受ECM微环境的机械和空间特性调节。同时，也存在一些关键差异，使血小板在细胞世界中独一无二——它们的大小、作为巨核细胞碎片的起源以及独特的αIIbβ3整合素——使其机械传感活动特别有趣。血小板结构上“简单”、无细胞核的性质，加上其高肌动蛋白浓度（占总蛋白的20%）和整合素密度[1]，似乎使其成为产生和传递机械力的理想选择。进一步的研究将增进我们对血小板机械生物学在止血和血栓形成中作用的理解，可能会带来新的诊断类别，即通过研究凝块的机械特性来确定出血风险，以及开发针对力转导信号通路以改变凝块稳定性的疗法。
