The adherence of platelets to adsorbed albumin by receptor-mediated recognition of binding sites exposed by adsorption-induced unfolding.
The adherence of platelets to adsorbed albumin by receptor-mediated recognition of binding sites exposed by adsorption-induced unfolding.
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通过受体介导的对吸附诱导解折叠暴露的结合位点的识别，血小板与吸附的白蛋白的粘附。
DOI：
10.1016/j.biomaterials.2009.10.017
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发表时间：
2010
期刊：
影响因子：
14
通讯作者：
Latour,RobertA
中科院分区：
文献类型：
--
作者：
Sivaraman,Balakrishnan;Latour,RobertA
尽管白蛋白 (Alb) 是最丰富的血浆蛋白，但它被认为对血小板不具有粘附性，因为它缺乏任何已知的用于结合血小板受体的氨基酸序列。最近的研究表明，血小板通过与其构象状态相关的机制粘附到吸附的白蛋白上。为了明确解决这个问题，我们使用圆二色性 (CD) 分光偏振法来表征从各种 Alb 溶液浓度中吸附在各种表面化学物质上的 Alb 构象，并使用乳酸脱氢酶 (LDH) 测定和扫描电子显微镜 (SEM) 检查血小板粘附。我们的结果证明，血小板通过受体介导的过程与吸附的白蛋白结合，白蛋白中的结合位点暴露和/或通过吸附诱导的蛋白质解折叠形成。最重要的是，超出解折叠的临界程度，血小板粘附水平与 Alb 中吸附诱导的解折叠密切相关。使用 Arg-Gly-Asp-Ser (RGDS) 肽阻断 Arg-Gly-Asp (RGD) 特异性血小板受体可显着抑制血小板对吸附的 Alb 的粘附，其中 Alb 和 Fg 的抑制程度和粘附血小板的形态相似。吸附的 Alb 层中精氨酸 (Arg) 残基的化学中和可显着抑制血小板与 Alb 的相互作用，表明 Arg 残基在介导血小板与 Alb 的粘附中发挥着重要作用。这些结果使人们更深入地了解介导血小板与吸附蛋白质相互作用的分子机制，以及如何控制这些相互作用以改善心血管应用生物材料的血液相容性。
Although albumin (Alb) is the most abundant plasma protein, it is considered to be non-adhesive to platelets, as it lacks any known amino acid sequences for binding platelet receptors. Recent studies have suggested that platelets adhere to adsorbed Alb by mechanisms linked to its conformational state. To definitively address this issue we used circular dichroism (CD) spectropolarimetry to characterize the conformation of Alb adsorbed on a broad range of surface chemistries from a wide range of Alb solution concentrations, with platelet adhesion examined using a lactate dehydrogenase (LDH) assay and scanning electron microscopy (SEM). Our results prove that platelets bind to adsorbed Alb through receptor-mediated processes, with binding sites in Alb exposed and/or formed by adsorption-induced protein unfolding. Most importantly, beyond a critical degree of unfolding, the platelet adhesion levels correlated strongly with the adsorption-induced unfolding in Alb. The blockage of Arg-Gly-Asp (RGD) specific platelet receptors using an Arg-Gly-Asp-Ser (RGDS) peptide led to significant inhibition of platelet adhesion to adsorbed Alb, with the extent of inhibition and morphology of adherent platelets being similar for both Alb and Fg. Chemical neutralization of arginine (Arg) residues in the adsorbed Alb layer inhibited platelet–Alb interactions significantly, indicating that Arg residues play a prominent role in mediating platelet adhesion to Alb. These results provide deeper insight into the molecular mechanisms that mediate the interactions of platelets with adsorbed proteins, and how to control these interactions to improve the blood compatibility of biomaterials for cardiovascular applications.
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影响因子：
14
作者：
Sivaraman, Balakrishnan;Latour, Robert A.
通讯作者：
Latour, Robert A.
DOI：
10.1021/la8036814
发表时间：
2009-03-03
期刊：
Langmuir : the ACS journal of surfaces and colloids
影响因子：
--
作者：
Sivaraman B;Fears KP;Latour RA
通讯作者：
Latour RA
DOI：
10.1021/la901885d
发表时间：
2009-08-18
期刊：
Langmuir : the ACS journal of surfaces and colloids
影响因子：
--
作者：
Fears KP;Sivaraman B;Powell GL;Wu Y;Latour RA
通讯作者：
Latour RA
通过选择性修饰富含精氨酸和 B 脱辅基蛋白中的精氨酰残基，抑制脂蛋白与成纤维细胞表面受体的结合。
影响因子：
4.8
作者：
Robert;W.;Mahley;Thomas;L.;Innerarity;E.;Pitas;Karl;H.;Weisgraber;Judith;BROwN
通讯作者：
BROwN
影响因子：
14
作者：
Grunkemeier, JM;Tsai, WB;Horbett, TA
通讯作者：
Horbett, TA