Department of Polymer Science, University of Akron, 170 University Ave, Akron, OH 44325, USA.
Department of Chemistry and Biochemistry, Rowan University, 201 Mullica Hill Rd, Glassboro, NJ 08028, USA.
Biomaterials. 2015 Jan;39:59-66. doi: 10.1016/j.biomaterials.2014.10.048. Epub 2014 Nov 15.
The critical role of the self-assembled structure of collagen in skeletal mineralization is long recognized, yet the angstrom to tens of nanometers length-scale nucleation mechanism of calcium phosphate mineral (Ca-Pi) remains unclear. Here, by constructing three-dimensional structure of collagen fibril, we report direct computational evidence of intrafibrillar Ca-Pi nucleation in the collagen matrix and illustrate the crucial role of charged amino acid sidechains of collagen molecules in nucleation. The all-atom Hamiltonian replica exchange molecular dynamics simulation shows that these charged sidechains are oriented toward the fibril "hole zones" and significantly template nucleation with amorphous Ca-Pi phase, ∼1.3-1.6 nm in size, thus explaining the empirical observations that Ca-Pi nucleates principally in these regions. We also show that the low water density of about 0.70 g cm(-3) in these zones may further benefit nucleation by lowering the enthalpic penalty for ion desolvation. This work provides insight, at the atomistic level, into the nucleation mechanism of bone crystals within a collagen matrix for understanding mineral deposition, interpreting mineralization experiments and guiding the design of new implantable materials.
胶原自组装结构在骨骼矿化中起着至关重要的作用，这一点早已得到公认，然而，钙磷矿物（Ca-Pi）在埃至数十纳米长度尺度上的成核机制仍不清楚。在这里，我们通过构建胶原原纤维的三维结构，报告了胶原基质中纤维内 Ca-Pi 成核的直接计算证据，并说明了胶原分子带电荷的氨基酸侧链在成核过程中的关键作用。全原子哈密顿复制交换分子动力学模拟表明，这些带电荷的侧链朝向原纤维的“空洞区”，并显著地对无定形 Ca-Pi 相进行模板成核，其尺寸约为 1.3-1.6nm，这解释了经验观察到的 Ca-Pi 主要在这些区域成核的现象。我们还表明，这些区域的水密度约为 0.70g cm(-3)，较低，这可能通过降低离子去溶剂化的焓罚来进一步有利于成核。这项工作从原子水平上深入了解了胶原基质中骨晶体的成核机制，有助于理解矿物质沉积、解释矿化实验以及指导新型可植入材料的设计。
