MATRIX BASED MINERAL ENAMEL-BIOMIMETICS

基于基质的矿物釉质仿生学

• 批准号: 7840752
• 负责人: Janet M. Oldak
• 金额: $ 0.82万
• 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: 2009-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7840752
• 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)：这项建议是基于设计和开发新的生物材料的需求，这些材料将用于牙釉质的修复和再生。本研究的主要目的是阐明牙釉质形成的分子机制，特别是细胞外成分：釉原蛋白、釉蛋白和成釉蛋白的超分子组装、结构和功能。长期的目标是开发仿生策略，在体外和无细胞系统中制造牙釉质类材料。我们的一般假设是，釉质中高度有序的碳化羟基磷灰石晶体是由蛋白质-蛋白质和蛋白质-矿物相互作用的复杂阵列形成的，主要由釉原蛋白纳米球与釉蛋白和/或成釉蛋白中的结构基元相互作用的超分子链组装控制。釉原蛋白独特的二级结构促进了釉原蛋白纳米球的形成和进一步组装成线性阵列。具体目的：1.研究釉原蛋白在体内和体外的纳米球链组装，并在体外阐明釉原蛋白序列中的二级结构偏好。确定32 kDa的釉蛋白和成釉蛋白片段的二级结构，并研究它们在体内和体外与釉原蛋白纳米球链的相互作用。3.研究非釉原蛋白存在下，釉原蛋白“链组件”与磷酸钙矿物的体外相互作用，并为牙釉质类纳米复合材料的制备建立仿生模型。总之，从我们在AIMS L-11中提出的研究中获得的主要分子机制将有助于我们理解牙釉质细胞外基质在体内的结构生物学，并将为设计和开发具有潜在应用于牙科和医疗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、蛋白质结构以及对牙釉质形成病理性的理解产生重大影响。