Isoexergonic Conformations of Surface-Bound Citrate Regulated Bioinspired Apatite Nanocrystal Growth.
Isoexergonic Conformations of Surface-Bound Citrate Regulated Bioinspired Apatite Nanocrystal Growth.
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DOI：
10.1021/acsami.6b04822
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发表时间：
2016-10
影响因子：
9.5
通讯作者：
Ziqiu Wang;Zhijun Xu;Weilong Zhao;Wei Chen;Toshikazu Miyoshi;Nita Sahai
中科院分区：
文献类型：
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作者：
Ziqiu Wang;Zhijun Xu;Weilong Zhao;Wei Chen;Toshikazu Miyoshi;Nita Sahai
骨和牙本质优异的生物力学性能在一定程度上是由羟基磷灰石(HAP)纳米晶在分层组装的胶原基质中独特的板状形态决定的。了解晶体生长的机制和形态对于合理设计用于骨科和牙科的仿生磷灰石纳米晶体是很重要的。长期以来，柠檬酸盐一直被认为可以调节磷灰石晶体的生长，但主要的问题是关于HAP结合的柠檬酸盐的构象以及相互作用的官能团和HAP表面位置的身份。在这里，我们对从埃到亚微米尺度的机制进行了全面的研究，通过详细关联高水平亚动力学模拟的结果，使用以实验为基准的力场和密度泛函理论计算，以及高分辨率电子显微镜、核磁共振光谱、溶液分析和热重分析的结果。随着柠檬酸浓度的增加，晶体形态由针状转变为片状。柠檬酸在HAP(100)面上的吸附比在(001)面上的吸附更强，从而导致了柠檬酸在[001]方向的择优生长和片状形貌。得到了两种截然不同的结合构象，分别涉及一个或两个末端羧基与三个或五个表面钙离子的相互作用，以及柠檬酸羟基和HAP表面之间的氢键。值得注意的是，尽管单结合羧基构象中的相互作用部位较少，但结构是等伸展的，因此两者都处于平衡状态。前一种构象的识别具有重要意义，因为它允许比传统假设的更大的吸附密度，并有助于解释柠檬酸盐在调节晶体形态时的浓度依赖关系。这些独特的结果首先是先进的偏动力学的应用，这是准确模拟离子材料所必需的技术，但很少用于生物材料和生物矿化领域，其次是计算、光谱和分析结果的详细关联。
The superior biomechanical properties of bone and dentin are dictated, in part, by the unique plate-like morphology of hydroxyapatite (HAP) nanocrysals within a hierarchically assembled collagen matrix. Understanding the mechanism of crystal growth and thus morphology is important to the rational design of bioinspired apatite nanocrystals for orthopedic and dental applications. Citrate has long been proposed to modulate apatite crystal growth, but major questions exist regarding the HAP-bound citrate conformations and the identities of the interacting functional groups and HAP surface sites. Here, we conducted a comprehensive investigation of the mechanism from the angstrom to submicrometer scale by detailed correlation of the results of high-level metadynamics simulations, employing force-fields benchmarked to experiment and density functional theory calculations with the results of high resolution transmission electron microscopy, nuclear magnetic resonance spectroscopy, solution analysis, and thermogravimetric analysis. Crystal morphology changed from needle- to plate-like with increasing citrate concentration. Citrate adsorbed more strongly on the HAP (100) face than on the (001) face, thus resulting in preferential growth in the [001] direction and the plate-like morphology. Two very different bound conformations were obtained, involving interactions of either one or both terminal carboxyl groups with three or five surface calcium ions, respectively, and a hydrogen bond between the citrate hydroxyl and the HAP surface. Remarkably, despite fewer interaction sites in the single bound carboxyl conformation, the structures were isoexergonic, so both exist at equilibrium. Identification of the former conformation is significant because it allows a greater adsorption density than is traditionally assumed and can help explain concentration-dependence of citrate in modulating crystal morphology. These unique results were enabled first by the application of advanced metadynamics, a technique necessary for the accurate simulation of ionic materials but which is rarely employed in the biomaterials and biomineralization fields and second by the detailed correlation of computational, spectroscopic, and analytical results.