Protein-mineral interactions at the organic-inorganic interface in biominerals

生物矿物质中有机-无机界面的蛋白质-矿物质相互作用

• 批准号: RGPIN-2022-03238
• 负责人: McKee, Marc
• 金额: $ 4.08万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=750712
• 关键词: Protein; mineral; interactions; organic; inorganic

Bones, teeth, otoconia, eggshells, snail shells, sea shells, corals, and many other biomineralized structures arise from synergistic interactions between co-existing organic (usually proteins) and inorganic mineral (often calcium-based) phases. These interactions produce hard, composite biological materials having specialized properties, largely attributable to hierarchically organized, supramolecular assemblies that provide a framework for remarkable biomineralized architectures. Negatively charged proteins within this organic framework (the extracellular matrix) may stabilize amorphous mineral precursor phases, or they may attain regulatory chemical complementarity by binding to lattice calcium at the organic-inorganic interface - mechanisms that influence crystal growth processes. It is hypothesized that the molecular precision of such organic-inorganic interfacial interactions regulates crystal growth to produce such hardened, biomineralized composite structures. My NSERC DG biomineralization research program focuses on specific biomolecules and proteins/peptides (notably osteopontin) that regulate calcium carbonate mineral growth (specifically here, the forms calcite and vaterite). Small biomolecules, amino acids, peptides and full-length proteins guide and regulate biomineralization. A common theme for calcium carbonate mineralization is that nanoparticles form within a confined, protein/peptide-rich reaction nanoenvironment, from which they crystallize and align over many length scales to build mesocrystals having occluded organics. This notion contrasts with classical crystallization theory which postulates ion-by-ion attachment. My biomineralization research program compares these scenarios by exploring fundamental principles of how relevant organics influence biomineralization. The short-term objectives for this proposal are to continue examining the extracellular regulatory mechanisms guiding Ca-carbonate biomineralization through three projects: i) reptile (gecko and snake) eggshell structure, ii) the interface (attachment) of avian and reptilian eggshell membrane fibers with the mineral of the shell, and iii) the determinants of synthetic, chiral helicoidal vaterite suprastructure growth (including simulations). Long-term objectives are to explore i) how diverse biomolecules influence Ca-carbonate growth and hierarchical assembly, and ii) how biomineral curvature (vs angulated facets) is produced in biology, particularly in shells. With new information from this research, we will understand key elements of biomineralization biology for calcium carbonate (particularly in eggshells, with implications for food safety in the case of the table egg) that might well cross over into other biomineralizing systems. Such a cross-over may potentially allow for tunable mineralization events in synthetic biomaterials with uses in tissue repair and tissue engineering applications, and for novel chiral materials with unique optical properties.

骨骼、牙齿、耳蜗、蛋壳、蜗牛壳、海贝壳、珊瑚和许多其他生物矿化结构都是由共存的有机（通常是蛋白质）和无机矿物（通常是钙基）相之间的协同相互作用产生的。这些相互作用产生了具有特殊特性的坚硬的复合生物材料，主要归因于分层组织的超分子组装，为显著的生物矿化结构提供了框架。在这个有机框架（细胞外基质）内带负电荷的蛋白质可以稳定无定形矿物前体相，或者它们可以通过在有机-无机界面与晶格钙结合来实现调节的化学互补-影响晶体生长过程的机制。据推测，这种有机-无机界面相互作用的分子精度调节晶体生长以产生这种硬化的生物矿化复合结构。我的NSERC DG生物矿化研究项目侧重于调节碳酸钙矿物生长的特定生物分子和蛋白质/肽（特别是骨桥蛋白）（具体来说，这里是方解石和水晶石的形式）。小生物分子、氨基酸、多肽和全长蛋白引导和调节生物矿化。碳酸钙矿化的一个共同主题是，纳米颗粒在一个受限的、富含蛋白质/肽的反应纳米环境中形成，在这个纳米环境中，它们结晶并排列在许多长度尺度上，以构建具有封闭有机物的介晶。这一概念与经典结晶理论相反，后者假定离子间的连接。我的生物矿化研究计划通过探索相关有机物如何影响生物矿化的基本原理来比较这些情况。本提案的短期目标是通过三个项目继续研究指导碳酸钙生物矿化的细胞外调节机制：i)爬行动物（壁虎和蛇）蛋壳结构，ii)鸟类和爬行动物蛋壳膜纤维与外壳矿物质的界面（附着），以及iii)合成手性螺旋形水晶石上层结构生长的决定因素（包括模拟）。长期目标是探索i)不同的生物分子如何影响碳酸钙的生长和分层组装，ii)生物矿物曲率（相对于成角的面）如何在生物学中产生，特别是在贝壳中。有了这项研究的新信息，我们将了解碳酸钙生物矿化生物学的关键因素（特别是在蛋壳中，在食用鸡蛋的情况下对食品安全的影响），这些因素可能会交叉到其他生物矿化系统中。这种交叉可能潜在地允许在组织修复和组织工程应用中使用的合成生物材料中可调节的矿化事件，以及具有独特光学性质的新型手性材料。