Surface-dependent expression in the platelet GPIb binding domain within human von Willebrand factor studied by atomic force microscopy
Surface-dependent expression in the platelet GPIb binding domain within human von Willebrand factor studied by atomic force microscopy
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DOI：
10.1016/j.thromres.2006.06.010
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发表时间：
2007-01-01
影响因子：
7.5
通讯作者：
Marchant, Roger E.
中科院分区：
文献类型：
--
作者：
Kang, Inkyung;Raghavachari, Madhusudan;Marchant, Roger E.
血浆蛋白如血管性血友病因子（vWF）在血栓形成表面的吸附可以诱导三级结构的构象变化，使血栓形成前功能表位暴露出来与血小板相互作用，导致血小板粘附和血栓形成。因此，了解vWF结构变化后血小板结合对了解血栓形成机制至关重要。本研究利用原子力显微镜（AFM）结合免疫金标记技术，研究了生理缓冲条件下吸附在两种不同血栓形成表面（疏水合成表面和胶原VI包被底物）上的vWF中血小板结合表位的可及性。我们的研究结果表明，与vWF在疏水合成表面上吸附相比，vWF在胶原VI上吸附时发生了糖蛋白Ib （GPIb）结合域的变化。本研究通过直接检测参与血栓形成的血浆蛋白的结构-功能关系，为了解表面诱导血栓形成的分子机制提供了新的方法基础。(c) 2006 Elsevier Ltd.版权所有。
Adsorption of plasma proteins such as von Willebrand factor (vWF) on thrombogenic surfaces can induce conformational changes in tertiary structure so that the prothrombotic functional epitopes are exposed for interactions with platelets, resulting in platelet adhesion and thrombus formation. Thus, understanding platelet binding following changes in the structure of vWF is critical in understanding the mechanisms of thrombogenesis. The present study examined the accessibility of platelet binding epitopes within vWF adsorbed on two different thrombogenic surfaces, a hydrophobic synthetic surface and collagen VI coated substrates, under physiological buffer conditions using atomic force microscopy (AFM) in combination with immunogold labeling. Our results demonstrated that the glycoprotein Ib (GPIb) binding domain in vWF undergoes changes when adsorbed on collagen VI compared to vWF on a hydrophobic synthetic surface. This study provides a basis for a novel approach to understand the molecular mechanisms of surface-induced thrombosis by directly examining the structure-function relationships of plasma proteins involved in the thrombus formation. (c) 2006 Elsevier Ltd. All rights reserved.