The role of collagen in bone apatite formation in the presence of hydroxyapatite nucleation inhibitors.
The role of collagen in bone apatite formation in the presence of hydroxyapatite nucleation inhibitors.
复制标题
在羟基磷灰石成核抑制剂存在下胶原蛋白在骨磷灰石形成中的作用。
作者：
骨是一种复合材料，其中胶原原纤维形成单轴取向磷灰石晶体高度组织化排列的支架。在胶原纤维的周期性67 nm横纹图案中，较不致密的40 nm长的间隙区被认为是磷灰石晶体从非晶相成核并随后生长的地方。这一过程被认为是由高酸性的非胶原蛋白指导的;然而，胶原基质在骨磷灰石矿化过程中的作用仍然未知。在这里，结合纳米级分辨率的低温透射电子显微镜和低温电子断层扫描与分子建模，我们表明，胶原蛋白的协同作用与羟基磷灰石成核抑制剂，积极控制矿化。靠近胶原分子C-末端的正净电荷促进无定形磷酸钙（ACP）浸润原纤维。此外，带电荷的氨基酸簇，在间隙和重叠区域，形成控制ACP转化成平行阵列的定向磷灰石晶体的成核位点。我们开发了一个模型，描述了胶原蛋白的结构，超分子组装和电荷分布可以控制矿化的羟基磷灰石成核抑制剂的存在下，通过该机制。
Bone is a composite material, in which collagen fibrils form a scaffold for a highly organized arrangement of uniaxially oriented apatite crystals. In the periodic 67 nm cross-striated pattern of the collagen fibril, the less dense 40-nm-long gap zone has been implicated as the place where apatite crystals nucleate from an amorphous phase, and subsequently grow. This process is believed to be directed by highly acidic non-collagenous proteins; however, the role of the collagen matrix during bone apatite mineralization remains unknown. Here, combining nanometre-scale resolution cryogenic transmission electron microscopy and cryogenic electron tomography with molecular modelling, we show that collagen functions in synergy with inhibitors of hydroxyapatite nucleation to actively control mineralization. The positive net charge close to the C-terminal end of the collagen molecules promotes the infiltration of the fibrils with amorphous calcium phosphate (ACP). Furthermore, the clusters of charged amino acids, both in gap and overlap regions, form nucleation sites controlling the conversion of ACP into a parallel array of oriented apatite crystals. We developed a model describing the mechanisms through which the structure, supramolecular assembly and charge distribution of collagen can control mineralization in the presence of inhibitors of hydroxyapatite nucleation.