Physical investigation and understanding of biomineralisation proteins and their use for the synthesis of new nanomaterials

近年来，科学和经济对纳米技术的兴趣日益浓厚。在此过程中，制造微小且高度定制的磁性颗粒或纳米磁铁是至关重要的。纳米磁铁有许多实际用途。从历史上看，它们被用于信息存储，如磁带和硬盘驱动器。最近，随着提供高密度数据存储的3D信息存储系统的发展，这种情况得到了扩展。人们对纳米磁铁的医学应用也很感兴趣。人们正在开发磁性颗粒，以在体内提供靶向药物。例如，如果药物在分子水平上与纳米磁铁相连，那么它们就可以通过磁铁定向到患者体内的特定部位。这使得药物可以被输送到特定的区域，而不会伤害身体的其他部分。同样，纳米磁铁也可以用于热疗。在被引导到特定的肿瘤部位后，磁性颗粒被加热以破坏肿瘤或激活药物。然而，随着纳米技术的发展，开发精确设计的纳米磁铁的需求也在增长。不同的应用需要不同形状和大小的颗粒以及不同的磁性。因此，控制纳米磁体的组成和尺寸成为研究人员的一个关键目标。生物矿化是指生物体产生骨骼等矿物质的过程。因为基因控制着生物矿化过程，所以产生的材料呈现出非常精确、均匀和复杂的结构，直至纳米级。此外，如果遗传学被理解，就有可能精确地改变生物矿化材料的性质。趋磁细菌在细菌细胞（称为磁小体）内的生物脂肪壳（或囊泡）内生物矿化高质量和均匀的氧化铁磁铁矿纳米颗粒。由于磁小体具有相当的均匀性和精确性，它们为生产高质量的纳米粒子提供了一条新颖而有吸引力的途径。然而，生物矿化方法对于商业生产可能是低效的，并且受限于细菌细胞施加的规格，几乎没有进一步修改的灵活性。一种在细菌中被发现参与制造纳米磁铁的蛋白质之前已经被提取出来，并被大量生产（表达）并用于磁性颗粒的化学沉淀。研究发现，即使在细菌细胞外的化学生产过程中，这种蛋白质也能控制颗粒的大小和形状。这项研究将从我们掌握的关于磁性细菌的遗传信息中识别出生物矿化蛋白，并通过表达这些蛋白，并将它们用于类似于先前研究的纳米颗粒的化学形成中，来单独研究这些蛋白。由此，我们将详细研究蛋白质如何使用显微镜，光谱学和衍射技术物理控制颗粒的大小和形状。这些将在蛋白质制造颗粒时对其进行研究，这样我们就能确定蛋白质的哪一部分负责控制颗粒的形成。有了这些信息，我们将开发一种化学/生物相结合的方法来制造纳米磁性颗粒。新方法将结合生物矿化提供的精度优势，以及化学合成提供的更高产量和更具可塑性的变化系统。此外，一旦确定了每种蛋白质的特定作用，就可以通过添加特定蛋白质和金属离子的配方来设计和定制颗粒。这将比生物系统更能控制粒子的特性。与单独使用细菌相比，这种仿生合成方法将允许在更大的规模上生产颗粒，并且更具商业可行性。

Scientific and economic interest in nanotechnology has grown in recent years. Within this the quest to produce tiny and highly tailored magnetic particles, or nanomagnets is crucial. Nanomagnets have a range of practical uses. Historically they have been used for information storage such as tapes and hard drives. Recently this has expanded, with the development of 3D information storage systems providing high density data storage. There is also much interest in the medical applications of nanomagnets. Magnetic particles are being developed to provide targeted medicine within the body. For example, if drugs are tied to nanomagnets at the molecular level then they can be directed by a magnet to specific sites within the patient. This allows a drug to be delivered to a specific area, without harming the rest of the body. Similarly, nanomagnets can be used in hyperthermic therapies. This is where, after being directed to specific tumour sites, magnetic particles are heated to either destroy a tumour or activate a drug. However, as nanotechnology grows, so too does the need to develop precisely engineered nanomagnets. Different applications demand different shapes and sizes of particles and different magnetic properties. Controlling the composition and dimensions of nanomagnets has therefore become a key goal of researchers. Biomineralisation is the process that occurs in living organisms to produce minerals such as bones. Because genetics control biomineralisation processes the materials produced exhibit very precise, uniform and intricate formations down to the nano-scale. Furthermore, if the genetics are understood it may be possible to change with precision the nature of biomineralised materials. Magnetotactic bacteria biomineralise high quality and uniform nanoparticles of the iron-oxide magnetite within biological fatty shells (or vesicles) within the bacterial cell (termed magnetosomes). Because magnetosomes exhibit considerable uniformity and precision they present a novel and attractive route to produce high quality nanoparticles. However, the biomineralisation method can be inefficient for commercial production and is restricted to the specifications imposed by the bacterial cell leaving little flexibility for further modifications. A protein found to be involved in making nanomagnets in the bacteria has previously been extracted, and mass produced (expressed) and used in a chemical precipitation of magnetic particles. The protein was found to control the particle's size and shape even in this chemical production outside the bacterial cell. This research will identify biomineralisation proteins from the genetic information we have about magnetic bacteria, and investigate these proteins individually by expressing then and using them in a chemical formation of nanoparticles similar to the previous study. From this we will study in detail how the protein physically controls the size and shape of the particles using microscopy, spectroscopy and diffraction techniques. These will study the proteins while they are making the particles, so we can identify which parts of the proteins are responsible for the control over formation. With this information we will develop a combined chemical/biological method of making nanomagnetic particles. The new method will combine the benefits of the precision offered by biomineralisation, with the higher yields and more malleable system with respect to variation, offered by chemical synthesis. Furthermore, once the specific role of each protein has been ascertained, particles can be designed and custom-made with the addition of a recipe of the specific proteins and metal ions. This will offer more control over the particles' characteristics than the biological system. This biomimetic synthetic method will allow for the production of particles on a larger, and more commercially viable, scale than if the bacteria alone were used.