MATRIX BASED MINERAL ENAMEL-BIOMIMETICS

基于基质的矿物釉质仿生学

• 批准号: 7904367
• 负责人: Janet M. Oldak
• 金额: $ 31.7万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7904367
• 关键词: Ameloblasts; Apatites; Biocompatible Materials; Biological; Biomimetics; Carbonates; Cell-Free System; Cells; Chemicals; Classification; Cloning; Communities; Complex; Cytoskeleton; Dental; Dental Enamel; Development; Enamel Formation; Extracellular Matrix; Gene Expression; Goals; Growth; Hydroxyapatites; In Vitro; Investigation; Learning; Medical; Minerals; Modeling; Molecular; Mutant Strains Mice; Nanosphere; Natural regeneration; Oral; Outcome; Pattern; Phenotype; Process; Protein Array; Proteinase 3; Proteins; Recombinants; Research Personnel; Scientist; Solid; Structural Protein; Structure; Tissues; Transgenic Organisms; amelogenin; base; biomineralization; calcium phosphate; craniofacial; design; enamelin; improved; in vivo; instrumentation; knockout animal; mineralization; molecular assembly/self assembly; nanocomposite; preference; programs; protein structure; repaired; structural biology

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.

描述（由申请人提供）：该提案基于对新生物材料的设计和开发的需求，这些新生物材料将用于修复和再生牙釉质。我们提出的研究的主要目的是阐明与牙齿牙釉质形成有关的分子机制，特别强调了额外细胞成分的超分子组件，结构和功能。氨基蛋白蛋白，搪瓷蛋白和杏仁蛋白。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类似搪瓷的材料。我们的总体假设是，牙釉质中高度有组织的碳酸羟基磷灰石晶体是通过蛋白质 - 蛋白质蛋白和蛋白质 - 矿物质相互作用的复杂阵列形成的，主要由氨基蛋白纳米球的超分子“链组件”控制，与酸膜酸膜酸中膜蛋白蛋白中的结构基序相互作用。氨基蛋白蛋白的独特二级结构促进了氨基蛋白素纳米球的形成及其进一步组装成线性阵列。具体目的：I。在体内和体外研究氨基蛋白蛋白的纳米球链组装，并在体外阐明氨基蛋白酶序列内的二级结构偏好。 ii。为了确定32KDA搪瓷蛋白和氨基蛋白酶片段的二级结构，并研究了它们与体内和体外氨基蛋白纳米磷酸链的相互作用。 iii。为了研究氨基蛋白蛋白“链组件”与非淀粉蛋白酶存在的体外磷酸钙矿物质的相互作用，并开发了用于制造搪瓷样纳米复合材料的仿生模型。总而言之：从我们在AIM中提出的研究中学到的主要分子机制L-LLL将有助于我们对体内搪瓷细胞外基质的结构生物学的理解，并将为在牙科和医疗领域具有潜在应用的改进材料的设计和开发提供稳固的基础。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搪瓷形成的理解产生重大影响。