Molecular Structure and Dynamics of Membranes

确定生物材料中的分子结构和动力学是现代生物物理学中最大的挑战之一，特别是在生理条件下。很少有实验技术可以在纳米尺度上获得结构和动力学性质。我们将使用先进的X射线和中子散射技术作为强大的工具来研究合成膜和生物材料中的结构、动力学和相互作用，研究的尺度可以达到纳米级，也可以达到纳秒级。 在拟议的研究项目中，我们将研究膜活性分子和多肽与模型脂膜的相互作用，它们在脂双层中的组织以及它们对脂类基质的影响。这些实验将在我们位于麦克马斯特的膜和蛋白质动力学实验室、位于Chalk River实验室的加拿大中子束中心以及美国和欧洲的国际中子源进行。 在胆固醇存在的情况下，木筏的形成是目前膜生物物理学的一个重要课题。我们将使用一种新的技术，即相干长度相关的中子衍射，研究在乙酰水杨酸(ASA)等分子存在下，随着膜组成的变化，木筏的形成和性质。这项新技术能够检测薄膜中的小的、纳米尺寸的和瞬变的区域，非常适合于研究这些木筏的性质和特性。 将研究含有乙醇的膜的分子结构和动力学，以更好地了解麻醉药跨膜扩散和功能所涉及的分子过程。通过使用氚标记和非弹性中子散射，可以确定乙醇和水分子的精确位置以及侧向和跨膜动力学。这将是这类实验的第一次，对于了解乙醇对运输和膜组织的影响很重要。 根据大小以及亲水和疏水性质，小分子可以被结合到疏水膜芯中，在脂头基团区域中分配，或者被限制在堆叠中的相邻双层之间。我们将研究核苷酸、阿司匹林和布洛芬分子与脂膜接触时的相互作用和组织，以及它们对脂类基质的影响。这些分子是研究脂膜中不同性质小分子的基本性质、相互作用和组织的很好的模型系统。我们的主要目标是这些分子的横向组织。对于ASA和核苷酸，我们将提供前所未有的结构信息。 生物材料的宏观性质通常由它们的基本构件，如蛋白质、甲壳素和角蛋白，组织成二级结构来决定。我们将研究生物材料，如蛋白质纤维、鱿鱼围栏、虫壳和头发，以研究这些分子在原位形成β-片状、纳米微晶和纳米纤维的组织。使用我们先进的X射线装置，我们将获得关于生物分子在不同二级结构和结构参数中组织的定量信息，这对于将分子组织与宏观功能联系起来是必不可少的。 这些项目是在现场确定膜和生物大分子的分子结构和动力学的重要步骤，它们在“自然”环境中处于相关的无序状态，并且是软物质和生物物理界普遍感兴趣的。

The determination of molecular structure and dynamics in biological materials is one of the greatest challenges in modern biophysics, in particular under physiological conditions. Few experimental techniques can access structural and dynamical properties on the nanometer scale. We will use advanced X-ray and neutron scattering techniques as powerful tools to study structure, dynamics and interactions in synthetic membranes and biomaterials down to nanometer length scales and up to nanosecond times. In the proposed research project we will study the interaction of membrane-active molecules and peptides with model lipid membranes, their organization within the lipid bilayer and their impact on the lipid matrix. The experiments will be conducted in our Laboratory for Membrane and Protein Dynamics at McMaster, the Canadian Neutron Beam Centre at Chalk River Laboratories and international neutron sources in the US and Europe. The formation of rafts in the presence of cholesterol is currently an important topic in membrane biophysics. We will study formation and properties of rafts as function of membrane composition and in the presence of molecules, such as acetylsalicylic acid (ASA), using a new technique, namely coherence length dependent neutron diffraction. This new technique is capable to detect small, nanometer sized and transient domains in membranes and ideally suited to study nature and properties of these rafts. The molecular structure and dynamics of membranes containing ethanol will be studied to better understand the molecular processes involved in trans-membrane diffusion and functioning of anesthetics. By using deuterium labeling and inelastic neutron scattering, the precise location and lateral and trans-membrane dynamics of ethanol and water molecules will be determined. These will be the first experiments of this kind and important to understand ethanol’s effect on transport and membrane organization. Depending on size and hydrophilic and hydrophobic properties, small molecules can be incorporated in the hydrophobic membrane core, partition in the lipid head group region or be confined between neighbouring bilayers in the stack. We will study the interaction and organization of nucleotides, ASA and ibuprofen molecules when in contact with lipid membranes and their impact on the lipid matrix. These molecules are excellent model system to investigate basic properties, interactions and organization of small molecules of different properties in lipid membranes. Our main objective is the lateral organization of these molecules. For ASA and nucleotides we will provide unprecedented structural information. Macroscopic properties of biomaterials are often determined by the organization of their elementary building blocks, such as proteins, chitin and keratin, into secondary structures. We will study biomaterials, such as protein fibres, squid pens and bug shells and hair, to study the organization of these molecules into beta-sheets, nano-crystallites and nano-fibrils in-situ. Using our advanced X-ray setup, we will obtain quantitative information about the organization of the biomolecules in different secondary structures and structural parameters, which is essential to relate molecular organization to macroscopic function. These projects are important steps towards the determination of molecular structure and dynamics of membranes and biological macromolecules in-situ, in their relevant, disordered state in their ‘natural’ environment, and of general interest to the soft-matter and biophysical community.