Silicon transport proteins: from membrane protein biophysics to bionanoscience

纳米技术将改变世界，开创高性能材料的新时代，应用于医疗保健、农业、能源、生物技术、计算、环境技术等领域。这场革命的核心支柱之一将是尺寸在1-100纳米量级的有机和无机材料。这些纳米尺寸的颗粒或纳米颗粒，由于其高的表面积与体积比和尺寸依赖的量子效应而表现出与块状材料不同的行为。许多纳米颗粒具有新颖或增强的光学、物理化学和磁性，将改进现有产品或为传感器、光学工具、生物标志物、治疗剂、催化剂和电子元件等新技术提供平台。这些进展将取决于合成方法，这些方法可以产生具有确定尺寸、形状和组成的稳定且不聚集的颗粒。然而，满足所有这些标准仍然是一个具有挑战性的技术目标，新的合成路线将是实现纳米颗粒技术的全部承诺的关键。有趣的是，生物学--可以被认为是功能性纳米技术的生动体现--提供了许多纳米材料的例子，这些材料是在温和的合成条件下从简单的前体非常精确地组装而成的。这就引出了一个假设：我们能否从生物学中学习新的技巧，从而在纳米颗粒合成中开拓新的前景？该提案将通过使用二氧化硅转运蛋白作为纳米级制造中的新型设备来解决这一假设。二氧化硅转运蛋白（SIT）是一个独特的完整膜蛋白家族，能够以高亲和力结合可溶形式的二氧化硅（二氧化硅酸）并将其穿过细胞膜转运到细胞中。这种活动被微观单细胞生物用来帮助在自己周围建造“玻璃房子”。然而，二氧化硅运输的确切细节目前还没有很好的理解。该提案旨在（i）发现SIT识别和运输二氧化硅的分子基础，以及（ii）将该理解应用于二氧化硅纳米颗粒的合成。这些目标中的第一个将通过体外研究SIT结构和功能来解决。这种经典的生物化学方法将为自然界中发现的唯一高亲和力蛋白质-二氧化硅相互作用提供前所未有的见解。第二个目标将通过将SIT蛋白重组成球形脂质囊泡并将二氧化硅转运到囊泡内部来实现，使得囊泡成为用于制备二氧化硅纳米颗粒的纳米级反应室。这些纳米反应器将具有对基质递送到生长的纳米颗粒的精细动力学控制以及对颗粒组成和合成环境的严格调节的优点。后一种益处对于复合或官能化纳米颗粒的受控合成将特别有用。因此，该提案提出了将膜蛋白科学与无机化学相结合的第一个例子，并为生物纳米科学提供了新的视野。它将为这一领域的一系列进一步发展提供一个平台。

Nanotechnology will change the world by ushering in a new era of high-performance materials with applications in healthcare, agriculture, energy, biotechnology, computing, environmental technology and more. One of the central pillars of this revolution will be organic and inorganic materials with dimensions on the order of 1-100 nanometres. These nano-sized particles, or nanoparticles, behave differently to bulk materials because of their high surface-to-volume ratio and size-dependent quantum effects. Many nanoparticles have novel or enhanced optical, physicochemical and magnetic properties and will either improve existing products or provide a platform for new technologies as sensors, optical tools, biomarkers, therapeutics, catalysts and electronic components. These advances will depend upon synthetic methods that can generate particles of a defined size, shape and composition that are stable and do not aggregate. However, fulfilling all of these criteria remains a challenging technical goal and new synthetic routes will be critical in realising the full promise of nanoparticle technology. Intriguingly, biology - which can be considered to be the living embodiment of functional nanotechnology - provides numerous examples of nanomaterials that are assembled very precisely from simple precursors under mild synthetic conditions. This leads to the hypothesis: can we learn new tricks from biology to develop fresh prospects in nanoparticle synthesis? The proposal will address this hypothesis by using silica transport proteins as novel devices in nanoscale fabrication. The silica transporters (SITs) are a unique family of integral membrane proteins that are able to bind a soluble form of silica, silicic acid, with high affinity and transport it across the cell membrane into the cell. This activity is used by microscopic single-celled organisms to help build 'glass houses' around themselves. However, the precise details of silica transport are currently not well understood. The proposal aims to (i) discover the molecular basis for silica recognition and transport by the SITs and (ii) apply that understanding in the synthesis of silica nanoparticles. The first of these aims will be addressed by in vitro studies of SIT structure and function. This classical biochemical approach will provide an unprecedented insight into the only high-affinity protein-silica interaction found in nature. The second aim will be met by reconstituting SIT proteins into spherical lipid vesicles and transporting silica into the vesicle interior, so that the vesicles become nanoscale reaction chambers for the preparation of silica nanoparticles. These nanoreactors will have the advantages of exquisite kinetic control over substrate delivery to the growing nanoparticle and stringent regulation of particle composition and the synthetic environment. This latter benefit will be particularly useful for the controlled synthesis of composite or functionalized nanoparticles. The proposal thus presents one of the first examples of combining membrane protein science with inorganic chemistry and offers new horizons in biological nanoscience. It will provide a platform for a range of further developments in this area.