MATRIX BASED MINERAL ENAMEL-BIOMIMETICS

描述（由申请人提供）：本提案基于设计和开发用于牙釉质修复和再生的新型生物材料的感知需求。我们提出的研究的主要目标是阐明参与牙釉质形成的分子机制，特别强调细胞外成分的超分子组装，结构和功能;釉原蛋白，釉蛋白和成釉蛋白。长期目标是开发仿生策略，用于在体外和无细胞系统中制造釉质样材料。我们的一般假设是，牙釉质中高度组织化的碳酸羟基磷灰石晶体是通过复杂的蛋白质-蛋白质和蛋白质-矿物质相互作用阵列形成的，主要由釉原蛋白纳米球与牙釉质蛋白和/或成釉蛋白内的结构基序相互作用的超分子“链组装”控制。釉原蛋白的独特二级结构促进了釉原蛋白纳米球的形成及其进一步组装成线性阵列。具体目标：一。研究釉原蛋白在体内和体外的纳米球链组装，并阐明体外釉原蛋白序列的二级结构偏好。二.确定32 kDa釉蛋白和成釉蛋白片段的二级结构，并研究它们与釉原蛋白纳米颗粒链的体内和体外相互作用。三.研究在非釉原蛋白存在下，釉原蛋白“链组装体”与磷酸钙矿物的体外相互作用，并开发用于制造釉质样纳米复合材料的仿生模型。总结：目的1 - 3中提出的主要分子机制将有助于我们理解体内釉质细胞外基质的结构生物学，并将为设计和开发具有潜在应用于牙科和医学领域的改进材料提供坚实的基础。此外，这项研究将对生物矿化、分子自组装、蛋白质结构以及对病理性釉质形成的理解产生重大影响。

DESCRIPTION (provided by applicant): This proposal is based on the perceived need for the design and development of new biomaterials that will be utilized in repair and regeneration of tooth enamel. The major objective of our proposed study is to elucidate the molecular mechanisms involved in the formation of dental enamel with a particular emphasize on the supramolecular assembly, structure and function of the extra cellular components; amelogenin, enamelin and ameloblastin. The long-term goal is to develop biomimetic strategies for the fabrication of enamel-like materials in in vitro and in cell free systems. Our general hypothesis is that the highly organized carbonated hydroxyapatite crystals in enamel are formed through complex arrays of protein-protein and protein-mineral interactions primarily controlled by the supramolecular "chain assembly" of amelogenin nanospheres interacting with the structural motifs within enamelin and/or ameloblastin. The formation of amelogenin nanospheres and their further assembly into linear arrays are promoted by the unique secondary structure of amelogenin proteins. Specific aims: I. To investigate the nanosphere chain assembly of amelogenin in vivo and in vitro, and to elucidate secondary structure preferences within the amelogenin sequence in vitro. II. To determine the secondary structures of the 32kDa enamelin and ameloblastin fragments and to investigate their interactions with the chains of amelogenin nanosphres in vivo and in vitro. III. To investigate the interaction of amelogenin "chain assemblies" with calcium phosphate minerals in vitro, in the presence of non-amelogenins, and to develop biomimetic models for fabrication of enamel-like nanocomposites. In Summary: The principal molecular mechanisms learned from our investigation proposed in aims l-lll will contribute to our understanding of the structural biology of enamel extracellular matrix in vivo, and will provide a solid ground for the design and development of improved materials with potential application in dental and medical field. Moreover, this study will have a significant impact on the field of biomineralization, molecular self-assembly, protein structure, and understanding of pathological enamel formation.