Interaction of nanoparticles with cell surfaces and membranes

这项拟议研究的目的是了解包裹着蛋白质和脂肪的纳米颗粒如何与培养中的细胞相互作用，并确定它们可能对细胞功能产生什么影响。提出这项工作的理由是，在过去的十年和未来的几十年里，将会有越来越多的新材料和产品的制备，这些材料和产品基于各种类型的纳米颗粒的使用，因为这种纳米颗粒具有新的和理想的性能。 了解纳米颗粒如何与生物材料相互作用，特别是与细胞相互作用，变得越来越重要，因为它们构成了生物体的基本构建单位。由于纳米颗粒可能被脂类(如果它们通过肺部进入)或蛋白质(如果它们进入血流)所覆盖，我们建议制备具有代表性的脂类和蛋白质涂层的纳米颗粒，以确定它们在细胞表面的结合位置，测量它们如何被细胞吸收，以及它们可能对细胞分裂、分化和形成组织的能力产生什么影响。 我们的建议是基于我们使用显微镜技术--特别是荧光显微镜和质谱学成像--来测量细胞上和细胞内纳米粒子的位置和数量的能力，以及我们观察细胞行为的经验。 如果成功，这项工作将提供关于纳米颗粒是否在细胞水平上干扰生物功能以及这是否对细胞有害的关键信息。这反过来将提供一个数据背景，可用于评估在未来产品中制备和使用纳米粒子的风险。

The objective of the proposed research is to understand how nanoparticles coated with proteins and lipids interact with cells in culture and to determine what effects they may have on the cellular functions. The rationale for the proposed work is that during the last decade and over decades to come, there will be more and more preparation of new materials and products that are based on use of nanoparticles of various types because the confer new and desirable properties. It is of increasing importance that we understand how nanoparticles interact with biological materials, in particular with cells, since they form the fundamental building unit of organisms. Since nanoparticles are likely to be covered by either lipids (if they enter through the lung) or proteins (if they enter into the blood stream), we propose to prepare nanoparticles with representative lipid and protein coatings, to determine where on cell surfaces they bind, to measure how they are taken up into the cells, and what effects they may have on the cells ability to divide, to differentiate, and to form tissues. We base the proposal on our ability to use microscopy techniques - particularly fluorescence microscopy and mass spectroscopy imaging - to measure locations and numbers of nanoparticles on and in cells, and our experience with looking at cell behaviour. If successful, this work will provide critical information about whether nanoparticles interfere with biological functions at the cellular level and whether this is harmful to the cells. This will in turn provide a background of data that can be used in assessing the risk of preparing and using nanoparticles in future products.