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New methods for the production and analysis of nanostructured self-assembled lipid mesophases with bicontinuous cubic topology as supported thin films

以双连续立方拓扑为支撑薄膜的纳米结构自组装脂质中间相的生产和分析新方法

基本信息

批准号：
EP/F036566/1
负责人：
Adam Squires
金额：
$ 37.03万
依托单位：
University of Reading
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2008
资助国家：
英国
起止时间：
2008 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FF036566%2F1
关键词：
New methods production analysis nanostructured

项目摘要

This research aims to extend our understanding of a newly-emerging class of materials known as QII or inverse bicontinuous cubic phases, by producing them in the form of thin films on flat substrates.When lipid molecules are mixed with water, they spontaneously assemble into a variety of ordered structures, including three different shapes of QII phase. These each contain branching networks of water channels, billionths of a metre in size, separated by a single lipid bilayer which is just like the one in a biological cell. We can precisely control the size of the water channels by varying the water content or temperature of the sample. By changing conditions further, we can also induce a phase transition from one shape into another.The controllable nanometer-scale size of the water channels, the large area of lipid bilayer packed into a small volume, and the fact that the bilayer contains an environment similar to a biological cell membrane, give QII phases a wide range of applications. In some, the bilayer is templated with another material, to make molecular sieves, electrodes or sensors. In other cases they may be used directly, as a vehicle for drug delivery, in biosensors based on membrane-bound proteins, or as a method of crystallizing membrane proteins in order to solve their structure. Furthermore, QII phases exist in nature, performing various biological roles; understanding their formation can help us to understand more generally what happens when cell membranes divide or fuse.There is much current research towards understanding the processes that produce and inter-convert QII phases, and towards developing new materials to exploit their properties. However, this research is hampered by the fact that experiments on QII materials are carried out on polydomain samples, where the regular 3D ordering only extends within a single micron-sized domain . A QII sample will contain billions of these domains, all oriented in random directions. This reduces the information obtained from experiments, introduces additional effects due to the boundaries between domains, and limits the technological potential of the material.Here, we aim to develop ways to produce a new form of QII sample, as thin films between 20 and 200nm thick. To achieve this we will begin by making a stack of bilayers supported on an extremely flat surface, using proven methods. Guided by phase diagrams that are already known for polydomain lipid samples, we will then change the sample environment to a different temperature and/or humidity, where it will undergo a transition into a QII phase. This will be a single domain in depth, and we will be able to apply, for the first time, a range of techniques that can investigate an area only one domain across. These include atomic force microscopy, which probes the surface of the sample with a resolution high enough to visualize single water channels in the QII phase, and x-ray scattering, which tells us the geometry, orientation and repeat spacing of the regular structures adopted. These new methods of sample preparation and analysis will produce a wealth of information on QII phases.First, we will be able to test unconfirmed models and predictions for the geometric pathways by which one phase turns into another. Secondly, we will find out how to control the sizes of the domains, and see the role that domain boundaries play in phase transitions. Thirdly, we will be able to produce and analyse asymmetric QII phases, structures that so far have never been made in a laboratory, where the two monolayers making up the bilayer differ in lipid composition. Such materials would have new properties and applications, and would offer better analogs of cell membranes. Finally, the work will form the basis for further projects, using supported thin films of QII as a better controlled system for electrochemistry, membrane protein research,and a range of other nanotechnological applications based on QII phases.

这项研究旨在通过在平板上以薄膜的形式产生QII或反双连续立方相来扩展我们对一类新出现的材料的理解。当脂质分子与水混合时，它们自发地组装成各种有序结构，包括三种不同形状的QII相。每个都包含水通道的分支网络，大小为十亿分之一米，由单一的脂双层隔开，就像生物细胞中的双层一样。我们可以通过改变样品的水含量或温度来精确控制水槽的大小。通过进一步改变条件，我们还可以诱导从一种形状到另一种形状的相变。水通道的纳米级可控尺寸，大面积的脂质双层包装成小体积，以及双层含有类似生物细胞膜的环境，这使得QII相具有广泛的应用前景。在一些情况下，双层被另一种材料作为模板，以制造分子筛、电极或传感器。在其他情况下，它们可以直接用作药物输送的载体，用于基于膜结合蛋白的生物传感器，或者作为一种使膜蛋白结晶以解决其结构的方法。此外，QII相存在于自然界中，发挥着不同的生物学作用；了解它们的形成可以帮助我们更广泛地了解细胞膜分裂或融合时发生的事情。目前有许多研究旨在了解QII相的产生和相互转化的过程，并开发新的材料来开发其特性。然而，QII材料的实验是在多域样品上进行的，这一事实阻碍了这项研究，其中常规的3D排序仅在单个微米大小的域内扩展。QII样本将包含数十亿个这样的领域，所有这些领域都是随机方向的。这减少了从实验中获得的信息，由于磁区之间的边界引入了额外的效应，并限制了材料的技术潜力。在这里，我们的目标是开发一种新形式的QII样品，比如厚度在20到200 nm之间的薄膜。为了实现这一点，我们将首先使用经过验证的方法，在极其平坦的表面上支撑一堆双层。在已知的多域类脂样品相图的指导下，我们将把样品环境改变到不同的温度和/或湿度，在那里它将经历到QII阶段的转变。这将是一个深入的单一领域，我们将首次能够应用一系列技术来调查仅跨越一个领域的区域。其中包括原子力显微镜，它以足够高的分辨率探测样品表面，足以显示QII相中的单个水通道；以及x射线散射，它告诉我们所采用的规则结构的几何形状、取向和重复间隔。这些新的样品制备和分析方法将产生大量有关QII阶段的信息。首先，我们将能够测试未经证实的模型和对一个阶段转变为另一个阶段的几何路径的预测。其次，我们将了解如何控制磁区的大小，并了解磁区边界在相变中所起的作用。第三，我们将能够产生和分析不对称QII相，这是迄今为止在实验室中从未制造过的结构，在实验室中，组成双层的两个单分子层的脂肪组成不同。这种材料将具有新的性能和应用，并将提供更好的细胞膜类似物。最后，这项工作将为进一步的项目奠定基础，使用QII的支持薄膜作为更好的控制系统，用于电化学、膜蛋白研究以及基于QII相的一系列其他纳米技术应用。