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没食子酰基调控的纤维蛋白原构象:解析单宁酸涂层上的抗血小板黏附作用

Galloyl groups-regulated fibrinogen conformation: Understanding antiplatelet adhesion on tannic acid coating.

作者信息

Yang Liwei, Han Lulu, Liu Qi, Xu Yige, Jia Lingyun

机构信息

Liaoning Key Laboratory of Molecular Recognition and Imaging, School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116023, PR China.

Liaoning Key Laboratory of Molecular Recognition and Imaging, School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116023, PR China.

出版信息

Acta Biomater. 2017 Dec;64:187-199. doi: 10.1016/j.actbio.2017.09.034. Epub 2017 Sep 25.

Abstract

UNLABELLED

Fibrinogen (Fgn) has been identified as the key protein in the process of biomaterial-induced platelet adhesion. We have recently reported a facile and effective method for constructing platelet-repellent surface using a natural polyphenol component tannic acid (TA). However, the mechanism by which the TA surface repels platelets was not fully understood. To address this issue, we investigated the adsorption of Fgn (amount and conformation) on four TA-functionalized surfaces with different amounts of galloyl groups and the potential for platelet adherence on these surfaces. The experimental results indicated that the four TA-functionalized surfaces adsorbed a similar amount of Fgn, but the conformation and bioactivity of the adsorbed Fgn and the subsequent platelet adherence were quite different among the surfaces. The TA surface with the most galloyl groups induced minimal changes in the conformation of Fgn, a result of the α and γ chains of the adsorbed Fgn being highly inactive on the surface, thus leading to an outstanding antiplatelet adhesion performance. With a decreased amount of galloyl groups, the activity of the α chain in the adsorbed Fgn remained unchanged, but the activity of the γ chain and the extent of platelet adhesion gradually increased. This work provided a new concept for controlling platelet adhesion on solid materials, and we envision that the TA film could have potential applications in the development of new blood-contacting biomaterials in the future.

STATEMENT OF SIGNIFICANCE

Reducing platelet adhesion on material surfaces is of tremendous scientific interest in the field of blood-contacting biomaterials, but it remains a big challenge due to the highly adhesive nature of the platelets. In this study, we demonstrated for the first time that tannic acid surface with abundant galloyl groups could induce minimal conformational changes of fibrinogen, eventually leading to an outstanding antiplatelet adhesion effect. In addition, the platelet adhesion response could be easily controlled through regulating the amount of galloyl groups on the surface. This work provided a new strategy for controlling platelet adhesion on solid materials, which was totally different from existing methods such as construction of physically patterned surfaces, modification of inert hydrophilic polymers or appending bioactive moieties to target surfaces.

摘要

未标注

纤维蛋白原(Fgn)已被确定为生物材料诱导血小板黏附过程中的关键蛋白。我们最近报道了一种使用天然多酚成分单宁酸(TA)构建抗血小板表面的简便有效方法。然而,TA表面排斥血小板的机制尚未完全明确。为解决这一问题,我们研究了Fgn在四种具有不同没食子酰基数量的TA功能化表面上的吸附情况(吸附量和构象)以及血小板在这些表面上的黏附潜力。实验结果表明,四种TA功能化表面吸附的Fgn量相似,但吸附的Fgn的构象和生物活性以及随后的血小板黏附在不同表面之间存在显著差异。没食子酰基数量最多的TA表面引起Fgn构象变化最小,这是由于吸附的Fgn的α链和γ链在表面上高度无活性,从而导致出色的抗血小板黏附性能。随着没食子酰基数量减少,吸附的Fgn中α链的活性保持不变,但γ链的活性和血小板黏附程度逐渐增加。这项工作为控制固体材料上的血小板黏附提供了一个新概念,我们设想TA膜在未来新型血液接触生物材料的开发中可能具有潜在应用。

意义声明

减少材料表面的血小板黏附在血液接触生物材料领域具有极大的科学意义,但由于血小板具有高度黏附性,这仍然是一个巨大挑战。在本研究中,我们首次证明具有丰富没食子酰基的单宁酸表面可诱导纤维蛋白原的构象变化最小,最终导致出色的抗血小板黏附效果。此外,通过调节表面没食子酰基的数量可以轻松控制血小板黏附反应。这项工作为控制固体材料上的血小板黏附提供了一种新策略,这与现有的方法如构建物理图案化表面、修饰惰性亲水性聚合物或在目标表面附加生物活性部分完全不同。

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