Maxwell Mhairi J, Dopheide Sacha M, Turner Samantha J, Jackson Shaun P
Australian Centre for Blood Diseases, Monash University, Prahran, Australia.
Arterioscler Thromb Vasc Biol. 2006 Mar;26(3):663-9. doi: 10.1161/01.ATV.0000201931.16535.e1. Epub 2005 Dec 29.
The platelet glycoprotein (GP) Ib/V/IX complex plays an important role in regulating the morphology of resting platelets and can induce shape change during adhesion to immobilized von Willebrand factor (vWf). In this study we have examined the effects of fluid shear stress on GPIb-dependent changes in platelet morphology during translocation on vWf.
We demonstrate that translocating platelets undergo a unique series of morphological changes in response to increasing fluid shear stress. Under moderately low shear conditions (600 s(-1)), initial shape change involved extension of membrane tethers and/or filopodia from the platelet surface. With increasing shear rate, platelets adopted a spherical morphology with numerous surface projections (1800 to 5000 s(-1)). At high wall shear rates (10000 to 20,000 s(-1)), translocating platelets retracted filopodia, developing a smooth ball-like appearance. These changes in morphology were dependent on reorganization of the actin and microtubule components of the cytoskeleton and were regulated by intracellular signaling processes linked to Src kinases. Functionally, alterations in platelet shape had a major effect on translocation dynamics in that conversion from discs to spheres resulted in a 3- to 8-fold increase in rolling velocity.
These studies demonstrate that platelets undergo shear-specific morphological changes during surface translocation on vWf that may serve to regulate translocation dynamics under flow.
血小板糖蛋白（GP）Ib/V/IX复合物在调节静息血小板形态方面发挥重要作用，并且在与固定化的血管性血友病因子（vWf）黏附过程中可诱导形状改变。在本研究中，我们检测了流体剪切应力对血小板在vWf上移位过程中依赖糖蛋白Ib的形态变化的影响。
我们证明，随着流体剪切应力增加，移位的血小板会经历一系列独特的形态变化。在适度低剪切条件（600 s⁻¹）下，初始形状改变包括从血小板表面伸出膜系链和/或丝状伪足。随着剪切速率增加，血小板呈现出具有大量表面突起的球形形态（1800至5000 s⁻¹）。在高壁剪切速率（10000至20000 s⁻¹）下，移位的血小板缩回丝状伪足，形成光滑的球状外观。这些形态变化依赖于细胞骨架中肌动蛋白和微管成分的重组，并受与Src激酶相关的细胞内信号传导过程调节。在功能上，血小板形状的改变对移位动力学有重大影响，因为从圆盘状转变为球状会导致滚动速度增加3至8倍。
这些研究表明，血小板在vWf表面移位过程中会经历剪切特异性的形态变化，这可能有助于调节流动状态下的移位动力学。
