MATRIX BASED MINERAL ENAMEL-BIOMIMETICS
基于基质的矿物釉质仿生学
基本信息
- 批准号:9902380
- 负责人:
- 金额:$ 46.15万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-05-01 至 2023-04-29
- 项目状态:已结题
- 来源:
- 关键词:AffectAmeloblastsAmelogenesisAnimal ModelBindingBiocompatible MaterialsBiologicalBiological ModelsBiomimeticsCell Culture TechniquesCell membraneCell-Matrix JunctionCellsChemical ModelsChemicalsComplexCrystal FormationCrystallizationDataDentalDental EnamelDental MaterialsEnamel FormationEventExonsExtracellular MatrixFuture GenerationsGeneticGoalsGrowthHydroxyapatitesIn SituIn VitroInvestigationKnowledgeLiposomesMediatingMineralsMolecularMorphologyMutationNMR SpectroscopyOutcomePathologicPatternPoint MutationProceduresProcessPropertyProteinsPublishingResolutionStructureTransmission Electron Microscopyameloblastinamelogeninbasebiomineralizationcalcium phosphatecell motilitydesignenamel matrix proteinsgene productin vivoinsightmalformationmigrationmineralizationmouse modelmutantnanoscalenoveloverexpressionpolarized cellrestorative material
项目摘要
Project Summary / Abstract
To achieve the long-term goal of restoring dental enamel, it is necessary to understand the fundamental
chemical and biological principles of extracellular matrix assembly and the manner they control mineral
nucleation and growth. There is still a large gap in our understanding of the underlying molecular mechanisms
by which enamel matrix proteins assemble and interact with cells to control nucleation and oriented growth of
hydroxyapatite crystals, and possibly cell movement and polarization. This is particularly true of ameloblastin
protein, which is the focus of our proposed study. The goal of this proposal is therefore to advance our
understanding of ameloblastin’s structure and function through a systematic investigation of its interactions
with different targets. We hypothesize that the highly organized carbonated hydroxyapatite crystals in enamel
continuously grow and form prismatic structures by means of complex ameloblastin-cell, ameloblastin-
amelogenin, and ameloblastin-mineral interactions. Two major aims are proposed to systematically examine
the above hypothesis by applying in vitro chemical models, cell culture and animal models for amelogenesis.
Aim I: To investigate ameloblastin-cell membrane interactions and identify the interacting domains using in
vitro synthetic liposomes and ameloblast-like cell culture model systems. We will design several mouse models
with point mutations in the interacting domains identified, and examine the consequence of these mutations on
enamel prismatic structure, ameloblast morphology, and the attachment of the cells to the matrix. We
hypothesize that ameloblastin interacts with ameloblast cells via a domain in the sequence encoded by exon 5
and functions to anchor the mineralizing extracellular matrix to the enamel-forming cells affecting cell
polarization, migration, and the formation of Tomes’ processes. Aim II: To investigate ameloblastin-amelogenin
interactions on the nanoscale in vivo and in vitro, and to identify their interacting domains using solution NMR
spectroscopy. We will study the dynamics of calcium phosphate mineralization events on the nanoscale when
ameloblastin is combined with amelogenin, using high resolution in situ atomic force (AFM) and Cryo-
transmission electron microscopy (TEM). We hypothesize that amelogenin and ameloblastin form
hetereomolecular entities that are functional during different stages of amelogenesis to control crystal
formation. We anticipate to gain more insight into the structure, assembly properties and function of
ameloblastin. We will define a novel cell- membrane- binding domain on ameloblastin protein. Novel protein-
protein-interacting domains on the ameloblastin and amelogenin sequences will be identified. The effect of
ameloblastin combined with amelogenin on mineralization will be elucidated and mineral-binding domains will
be identified. These studies will advance understanding of the molecular function of ameloblastin in enamel
biomineralization and will contribute to our efforts to fabricate synthetic enamel.
项目摘要/摘要
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Janet M. Oldak其他文献
Janet M. Oldak的其他文献
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{{ truncateString('Janet M. Oldak', 18)}}的其他基金
Monetite-Apatite Phase Transformation for an Enamel-Like Restorative Material
类牙釉质修复材料的三斜磷灰石-磷灰石相变
- 批准号:
9894790 - 财政年份:2019
- 资助金额:
$ 46.15万 - 项目类别:
A Peptide-Based Biomineralization Strategy for Tooth Repair
基于肽的牙齿修复生物矿化策略
- 批准号:
10084287 - 财政年份:2019
- 资助金额:
$ 46.15万 - 项目类别:
A Peptide-Based Biomineralization Strategy for Tooth Repair
基于肽的牙齿修复生物矿化策略
- 批准号:
10328496 - 财政年份:2019
- 资助金额:
$ 46.15万 - 项目类别:
TENTH INTERNATIONAL CONFERENCE ON THE CHEMISTRY AND BIOLOGY OF MINERALIZED TISSUE
第十届国际矿化组织化学与生物学会议
- 批准号:
7914912 - 财政年份:2010
- 资助金额:
$ 46.15万 - 项目类别:
INTRINSICALLY DISORDERED PROTEINS IN BIOMINERALIZATION
生物矿化中的本质无序蛋白质
- 批准号:
8119445 - 财政年份:2009
- 资助金额:
$ 46.15万 - 项目类别:
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