Molecular Structure and Dynamics of Membranes

确定生物材料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特性。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的结构，动力学和相互作用，直到纳米长度尺度和纳秒时间。在本研究项目中，我们将研究膜活性分子和肽与模型脂质膜的相互作用，它们在脂质双分子层中的组织以及它们对脂质基质的影响。实验将在麦克马斯特的膜和蛋白质动力学实验室、乔克河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。在胆固醇存在下筏的形成是目前膜生物物理学的一个重要课题。我们将研究筏的形成和性质作为膜组成的函数和存在的分子，如乙酰水杨酸（ASA），使用一种新的技术，即相干长度相关的中子衍射。这项新技术能够检测膜中的小的、纳米尺寸的瞬态结构域，非常适合研究这些筏的性质和性能。我们将研究含乙醇膜的分子结构和动力学，以更好地了解麻醉药物跨膜扩散和功能的分子过程。通过氘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横向和跨膜动力学。这将是这种类型的第一次实验，对了解乙醇对运输和膜组织的影响很重要。根据大小和亲疏水性质的不同，小分子可以被纳入疏水膜核心，在脂质头基团区域划分或被限制在堆栈中相邻的双层之间。我们将研究核苷酸、ASA和布洛芬分子与脂质膜接触时的相互作用和组织及其对脂质基质的影响。这些分子是研究脂质膜中不同性质小分子的基本性质、相互作用和组织的良好模型系统。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。生物材料的宏观特性通常是由它们的基本构建块（如蛋白质、几丁质和角蛋白）组成二级结构决定的。我们将研究生物材料，如蛋白质纤维、鱿鱼笔、虫壳和头发，研究这些分子在β片、纳米晶体和纳米原纤维中的原位组织。利用我们先进的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的组织的定量信息，这是将分子组织与宏观功能联系起来的必要条件。这些项目是朝着确定膜和生物大分子的分子结构和动力学的重要步骤，在他们的“自然”环境中，在他们相关的，无序的状态，以及软物质和生物物理社区的普遍兴趣。

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.