MATRIX-BASED MINERAL (MBM) ENAMEL BIOMIMETICS

描述(申请人提供)：这项建议的目的是促进我们对形成过程中所涉及的基本分子机制的理解。 重点介绍了牙釉质的纳米结构和功能 分泌期釉质基质的蛋白质及其所含的 釉原蛋白是“纳米球”。我们假设，这样的理解将导致 创造牙釉质的仿生策略的未来发展 矿物材料。我们的一般假设是：釉原蛋白一级结构 定义釉原蛋白四元结构(纳米球)，这反过来又直接 促进后成核的釉质基质超分子构型 碳酸化羟基磷灰石釉质晶体的生长。这种生物矿化作用 这一过程通过两个主要的分子机制来影响：(1) 釉原蛋白-蛋白质相互作用导致牙釉质的组织 细胞外基质和定义空间环境，以及，(2) 蛋白质-矿物质相互作用，抑制过早的晶体-晶体融合和 促进釉质晶体的受控定向生长。我们建议 为了检验这一假说，有以下具体目的：1.使用 重组和天然釉质蛋白(釉原蛋白、釉蛋白和 成釉蛋白)，以确定定义蛋白质的相互作用的性质 溶液中的自组装和纳米球矩阵体系结构，位于 分子水平。2.使用重组和天然釉质蛋白来定义，在 釉原蛋白凝胶的超分子水平和超微结构 在釉质蛋白和成釉蛋白存在和不存在的情况下，体外形成基质。3.磷灰石和磷酸八钙的表征 合成釉原蛋白凝胶中晶体的生长、形态和取向 在没有和存在非釉原蛋白的情况下的基质。4.刻画 釉原蛋白和非釉原蛋白对磷灰石和八钙的影响 溶液中晶体的生长形态，决定了分子的性质 蛋白质与这些磷酸钙晶体的相互作用。5.至 在超分子水平上定义的超结构结构 在体内研究釉原蛋白-凝胶基质，并确定釉质蛋白的定位及其与矿物相的关系。总而言之，考虑到牙齿 牙釉质作为一种可以用仿生策略修复的组织，它是 设想从这些拟议研究中获得的知识和信息 将为材料科学家设计和开发提供灵感 新型和改进的生物材料。

DESCRIPTION (provided by applicant):The goal of this proposal is to advance our understanding of the fundamental molecular mechanisms involved in the formation of dental enamel, with an emphasize on the nanoscale structure and function of the proteins of the secretory stage enamel matrix and its contained arrays of amelogenin "Nanospheres." We postulate that such understanding will lead to the future development of biomimetic strategies for the creation of enamel-like mineral materials. Our general hypothesis is: Amelogenin primary structure defines amelogenin quaternary structures (nanospheres) which in turn direct enamel matrix supramolecular architecture facilitating the postnucleation growth of carbonated hydroxyapatite enamel crystals. This biomineralization process is affected through two major molecular mechanisms: (1) amelogenin-protein interactions resulting in the organization of the enamel extracellular matrix and defining the spatial environment, and, (2) protein-mineral interactions, inhibiting premature crystal-crystal fusion and promoting the controlled and oriented growth of the enamel crystals. We propose to examine this hypothesis with the following Specific Aims: 1. Using recombinant and native enamel proteins (amelogenins, enamelins and ameloblastin), to identify the nature of the interactions which define protein self-assembly in solution and the nanosphere matrix architecture, at the molecular level. 2.Using recombinant and native enamel proteins to define, at the supramolecular level, the ultrastructural architecture of amelogenin-gel matrices formed in vitro in the presence and absence of enamelins and ameloblastin proteins. 3. To characterize apatite and octacalcium phosphate crystal growth, morphology and orientation within synthetic amelogenin gel matrices in the absence and presence of the non-amelogenins. 4. To characterize the effects of amelogenin and non-amelogenins on apatite and octacalcium crystal growth morphology in solution, determining the nature of molecular interactions of the proteins with these calcium phosphate crystals. 5. To define, at the supramolecular level, the ultra structural architecture of amelogenin-gel matrix in vivo and to determine the localization of enamel proteins and their relation to the mineral phase. In summary, considering tooth enamel as a tissue that may be restored with biomimetic strategies, it is envisaged that the knowledge and information gained from these proposed studies will provide the inspiration for material scientists to design and develop novel and improved biomaterials.