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-2016-05031
• 负责人: McKee, Marc
• 金额: $ 2.4万
• 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: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=615454
• 关键词: Protein; mineral; interactions; organic; inorganic

Bones, teeth, otoconia, eggshells, snail and sea shells, corals and many other biomineralized structures in the plant and animal kingdoms arise from synergistic interactions between co-existing organic (usually proteins) and inorganic mineral phases. These composites have specialized properties, and hierarchically organized supramolecular assemblies that provide a framework for biomineralization. Negatively charged proteins may attain regulatory chemical complementarity by binding to mineral calcium at the organic-inorganic interface − a mechanism to influence crystal growth processes. It is hypothesized that the molecular precision of such organic-inorganic interfacial interactions regulates crystal growth. My biomineralization research program focuses on specific proteins/peptides (notably osteopontin) that regulate mineral growth. Intriguingly, amino acids, peptides and full-length proteins can be occluded within mineral crystals. Related to this, biomineralization can proceed initially through assembly of amorphous precursor nanoparticles forming within a confined, protein/peptide-rich reaction nanoenvironment. Within these nanoparticle domains, transformation towards a crystalline phase may occur over different length scales such that single crystals (by diffraction) can actually consist of aligned mineral nanoparticles, the fusion of which builds mesocrystals having occluded organics. This notion is in stark contrast to classical crystallization theory which postulates ion-by-ion attachment. My biomineralization research program compares these scenarios by exploring fundamental principles of how organics (amino acids, and relevant peptides and proteins) influence biomineralization. We will compare two polymorphs of calcium carbonate crystals (calcite and vaterite) grown in the presence of osteopontin protein/peptides/amino acids to two biomineralized structures − avian eggshell and mouse inner ear otoconia. To study the growth of calcium carbonate crystals in the presence of these organics, a variety of morphological, biochemical, immunochemical, cell biological/molecular, and characterization techniques will be used including: electron microscopy, atomic force microscopy, confocal microscopy, X-ray and electron diffraction, Canadian Light Source synchrotron analyses, Raman spectroscopy, immunocytochemistry on mouse otoconia, in vitro cell culture and crystal growth systems, mass spectroscopy, and RosettaSurface energy-minimization computational simulations. With this mechanistic biomineralization information on how proteins and peptides bind to crystals to regulate their growth, we will be well-positioned to create tunable mineralization events that advance biomaterials and tissue engineering applications to the benefit of Canadians and citizens worldwide.

骨骼、牙齿、耳蜗、蛋壳、蜗牛和海贝壳、珊瑚和许多其他植物和动物王国的生物矿化结构都是由共存的有机（通常是蛋白质）和无机矿物相之间的协同作用产生的。这些复合材料具有特殊的性质，并且具有分层组织的超分子组装，为生物矿化提供了框架。带负电荷的蛋白质可能通过在有机-无机界面与矿物钙结合而获得调节的化学互补-这是一种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的生长。我的生物矿化研究项目侧重于调节矿物质生长的特定蛋白质/肽（特别是骨桥蛋白）。