Molecular simulation to characterize the adsorption behavior of a fibrinogen γ-chain fragment
Molecular simulation to characterize the adsorption behavior of a fibrinogen γ-chain fragment
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DOI：
10.1021/la0478346
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发表时间：
2005-02-01
期刊：
影响因子：
3.9
通讯作者：
Latour, RA
中科院分区：
文献类型：
--
作者：
Agashe, M;Raut, V;Latour, RA
植入物会引起身体的炎症反应，即使它们是化学惰性和无毒的。研究表明，炎症过程中一个至关重要的先例事件是纤维蛋白原（Fg）在植入物表面的自发吸附，这通常伴随着吞噬细胞的存在。吞噬细胞整合素Mac-1与纤维蛋白原γ链中的两个短序列gamma190-202和gamma377-395之间的相互作用可能部分解释了植入物表面的吞噬细胞积累。这两个序列被认为形成了一个整合素结合位点，当Fg处于可溶性结构时，该位点无法进入，但在吸附后，可能由于吸附引起的构象变化，该位点可以与Mac-1结合。本研究的目的是通过分子动力学模拟Fg的γ链片段在自组装单层（SAM）表面呈现不同类型的表面化学，从理论上探讨这种可能性。使用GROMACS软件包在显式溶剂化环境中进行5ns时间内的分子模拟。模拟了纤维蛋白原γ链在五种SAM表面的吸附。模拟结果表明，该蛋白片段在不同的表面化学物质上表现出明显不同的吸附行为。尽管轨迹文件显示，在模拟的时间框架内，该蛋白质片段没有发生显着的构象变化，但可以预测，在稳定在各种首选方向之前，蛋白质确实在表面上经历了大量的旋转和平移运动。这表明，表面诱导的蛋白质结构构象变化的动力学可能比取向变化的动力学慢得多，因此，在发生大的构象变化之前，吸附热力学原理可以用来指导吸附蛋白质在表面上的确定方向。这一发现可能对生物材料的表面设计非常重要，因为它表明表面化学可以潜在地用于直接控制吸附蛋白质的方向，以一种方式呈现或隐藏蛋白质结构中包含的特定生物活性位点，从而提供一种机制来控制细胞对吸附蛋白质层的反应。
Implants invoke inflammatory responses from the body even if they are chemically inert and nontoxic. It has been shown that a crucial precedent event in the inflammatory process is the spontaneous adsorption of fibrinogen (Fg) on implant surfaces, which is typically followed by the presence of phagocytic cells. Interactions between the phagocyte integrin Mac-1 and two short sequences within the fibrinogen gamma chain, gamma190-202 and gamma377-395, may partially explain phagocyte accumulation at implant surfaces. These two sequences are believed to form an integrin binding site that is inaccessible when Fg is in its soluble-state structure but then becomes available for Mac-1 binding following adsorption, presumably due to adsorption-induced conformational changes. The objective of this research was to theoretically investigate this possibility by using molecular dynamics simulations of the gamma-chain fragment of Fg over self-assembled monolayer (SAM) surfaces presenting different types of surface chemistry. The GROMACS software package was used to carry out the molecular simulations in an explicit solvation environment over a 5 ns period of time. The adsorption of the gamma-chain of fibrinogen was simulated on five types of SAM surfaces. The simulations showed that this protein fragment exhibits distinctly different adsorption behavior on the different surface chemistries. Although the trajectory files showed that significant conformational changes did not occur in this protein fragment over the time frame of the simulations, it was predicted that the protein does undergo substantial rotational and translational motions over the surface prior to stabilizing in various preferred orientations. This suggests that the kinetics of surface-induced conformational changes in a protein's structure might be much slower than the kinetics of orientational changes, thus enabling the principles of adsorption thermodynamics to be used to guide adsorbing proteins into defined orientations on surfaces before large conformational changes can occur. This finding may be very important for biomaterial surface design as it suggests that surface chemistry can potentially be used to directly control the orientation of adsorbing proteins in a manner that either presents or hides specific bioactive sites contained within a protein's structure, thereby providing a mechanism to control cellular responses to the adsorbed protein layer.