Nanostructured biomaterials: investigating hierarchical calcite crystal formation

纳米结构生物材料：研究分级方解石晶体形成

• 批准号: BB/M029611/1
• 负责人: Fabio Nudelman
• 金额: $ 33.01万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM029611%2F1
• 关键词: Nanostructured; biomaterials; investigating; hierarchical; calcite

Living organisms are well known to produce complex mineralised structures that are used for a wide variety of functions, such as navigation, support and protection of soft parts of the body, among others. The formation of such mineralised tissues requires an intricate biological machinery that controls all steps involved in mineralization, from controlling the transport of ions to the mineralisation site to controlling crystal nucleation, growth and morphology and the formation of micron- and macro-sized mineralized tissues. To date, no study could address how all these factors are integrated during the biomineralisation process. As such, what is missing is a fundamental understanding on how cells control processes occurring at different stages and lengths scales, going from the transport of ions to the mineralisation site to crystal nucleation, growth and assembly of the crystals into a hierarchical multi-crystalline mineralised tissue. This issue in the long term, will provide biologists and chemists with new tools to design and synthesise advanced materials with potential applications for biomedical, industrial and technological applications.The aim of this project is to understand how cells control the formation of mineralized tissue, from the first crystals that are formed at the nano-scale, to the mature mineral that is composed of crystals organised in a higher-order structure. For this, we will investigate the formation of coccolith scales made of calcite that are produced by the unicellular marine algae Emiliana huxleyi and Coccolithus pelagicus. These unicellular provide unique models in which all stages in mineralisation, occurring at all length scales - from the onset of mineral formation to the mature mineral - can be investigated in a single system and in a time-resolved manner to elucidate how they contribute to the formation and overall properties of the biomineral.To achieve this aim, we will combine confocal microscopy, cryo-scanning electron microscopy and cryo-transmission electron microscopy. These techniques will provide detailed structural and morphological information on all stages of mineral formation. We will focus on the following aspects:1- Understand the mechanisms of transport of CaCO3 to the coccolith vesicle, which is the mineralisation site. We will combine live-cell imaging and cryo-scanning electron microscopy, to visualise the transport of calcium ions to the mineralization site during mineral formation;2- Elucidate the mechanisms of control over crystal nucleation, growth and morphology. We will address how oriented nucleation is controlled by an organic template, and how crystal morphology is shaped during coccolith formation. This objective will be achieved using cryo-transmission electron microscopy (cryoTEM) to characterize the different stages of coccolithogenesis in situ;3- Understand the nature of the initially deposited mineral. We hypothesise that the mineral is initially deposited as a non-crystalline precursor which later crystallises into calcite. We intend to characterise this initial mineral phase and understand its role in the formation of coccolith structures. This objective will be achieved combining cryoTEM with Raman spectroscopy to characterise the initially deposited mineral phase, and follow the development of crystallinity.Taken together, this study will be the first time in which all stages in biomineral formation will be visualized in a single system. It will reveal unprecedented information on how living organisms control and tailor the size, morphology and construction of complex mineralized structures at all length scales. In the long term, these results will lead to new strategies for the synthesis of novel materials with controllable size, structure and material properties for several industrial and technological applications.

众所周知，活的生物体会产生复杂的矿化结构，用于各种功能，如导航、支持和保护身体的软组织等。这种矿化组织的形成需要一种复杂的生物机制来控制矿化涉及的所有步骤，从控制离子到矿化地点的运输到控制晶体成核、生长和形态以及微米和宏观矿化组织的形成。到目前为止，还没有研究能够解决所有这些因素在生物矿化过程中是如何整合的。因此，缺乏对细胞如何控制在不同阶段和不同长度尺度上发生的过程的基本了解，从离子到矿化位置的运输到晶体的成核、生长和组装成分层的多晶体矿化组织。从长远来看，这一问题将为生物学家和化学家提供新的工具，以设计和合成具有潜在应用于生物医学、工业和技术应用的先进材料。该项目的目的是了解细胞如何控制矿化组织的形成，从纳米尺度上形成的第一个晶体，到以更高级别结构组织的晶体组成的成熟矿物。为此，我们将研究由方解石制成的球藻鳞片的形成，这些球藻是由单细胞海藻Emily huxleyi和Coccolisus pelagicus产生的。这些单细胞提供了独特的模型，在这些模型中，发生在所有长度尺度上的矿化的所有阶段-从矿物形成的开始到矿物的成熟-可以在一个单一的系统中以时间分辨的方式进行研究，以阐明它们如何对生物矿物的形成和整体性质做出贡献。为了实现这一目标，我们将结合共聚焦显微镜、低温扫描电子显微镜和冷冻透射电子显微镜。这些技术将提供有关矿物形成所有阶段的详细结构和形态信息。我们将着重于以下几个方面：1-了解CaCO3向球石小泡的运输机制，球石小泡是矿化部位。我们将结合活细胞成像和低温扫描电子显微镜，可视化钙离子在矿物形成过程中向矿化地点的运输；2-阐明控制晶体成核、生长和形态的机制。我们将讨论有机模板如何控制定向成核，以及球石形成过程中晶体形态是如何形成的。这一目标将使用低温透射电子显微镜(CryoTEM)在原位表征球石形成的不同阶段；3-了解初始沉积矿物的性质。我们假设这种矿物最初是以非晶态前体的形式沉积下来的，后来又结晶成方解石。我们打算对这一初始矿物相进行表征，并了解其在球石结构形成中的作用。这一目标将结合CryoTEM和拉曼光谱来表征初始沉积的矿物相，并跟随结晶学的发展。综合起来，这项研究将首次在单一系统中可视化生物矿物形成的所有阶段。它将揭示关于生物如何控制和定制所有长度尺度上复杂矿化结构的大小、形态和结构的前所未有的信息。从长远来看，这些结果将为合成尺寸、结构和材料性能可控的新型材料带来新的战略，用于多种工业和技术应用。

项目成果

Disordered Filaments Mediate the Fibrillogenesis of Type I Collagen in Solution.

无序的细丝介导溶液中 I 型胶原蛋白的纤维形成。

• DOI: 10.1021/acs.biomac.0c00667
• 发表时间: 2020
• 期刊: Biomacromolecules
• 影响因子: 6.2
• 作者: McCluskey AR

Formation of Fluorohydroxyapatite with Silver Diamine Fluoride

• DOI: 10.1177/0022034517709738
• 发表时间: 2017-09-01
• 期刊: JOURNAL OF DENTAL RESEARCH
• 影响因子: 7.6
• 作者: Mei, M. L.;Nudelman, F.;Chu, C. H.
• 通讯作者: Chu, C. H.

Micron-sized biogenic and synthetic hollow mineral spheres occlude additives within single crystals.

• DOI: 10.1039/d1fd00095k
• 发表时间: 2022-07-14
• 期刊: Faraday discussions
• 影响因子: 3.4

Morphological development of Pleurochrysis carterae coccoliths examined by cryo-electron tomography.

通过冷冻电子断层扫描检查侧金藻球石的形态发育。

• DOI: 10.1016/j.jsb.2020.107476
• 发表时间: 2020
• 期刊: Journal of structural biology
• 影响因子: 3
• 作者: Walker JM

Effect of Ag Co-catalyst on TiO2-Cu2O nanocomposites structure and apparent visible photocatalytic activity.

• DOI: 10.1016/j.jenvman.2020.110175
• 发表时间: 2020-04
• 期刊: Journal of environmental management
• 影响因子: 8.7
• 作者: D. Nagy;Cong Chao;Bartosz Marzec;F. Nudelman;M. Ferrari;Xianfeng Fan