Structural studies of atomic interactions in membranes: bridging the gap between physics and membrane biology

膜中原子相互作用的结构研究：弥合物理学和膜生物学之间的差距

• 批准号: EP/J002615/1
• 负责人: Sylvia McLain
• 金额: $ 171.49万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FJ002615%2F1
• 关键词: Structural; studies; atomic; interactions; membranes

The focus of this work is observe the atomic and molecular interactions between molecules which comprise cell membranes. Cellular membranes are the gate-keepers of life. Life has evolved from single-celled organisms to more complex multi-cellular organisms partially because of the compartmentalization of cell membranes. In the last century one of the great challenges was to decode DNA - the molecular blueprint for life. In the next century one of the greatest challenges is to understand how membranes are formed and function; as they are not only everywhere but are also necessary to sustain life. Cell membranes control what can go into and out of the cell, the so-called 'molecular traffic' acting as gate-keepers. This role is important in controlling disease, disease and nutritional balance in different parts of the human body. This research proposes to look at the interactions between the molecules which make up biological membranes on the atomic scale, where one can see how individual atoms in different molecules interact with one another. This is important because it reveals the details of interactions and can inform us about how these interactions take place. The techniques which will be used to see the atomic structure of membranes are neutron scattering techniques using the UK ISIS neutron facilities which are located at Rutherford Appleton Laboratories in Oxfordshire (UK) and managed by the UK government funded Science and Technology Facilities Council (STFC). Measurements of these molecules using neutrons shows the details of interactions between the different atoms present. Another technique which will be used is Nuclear Magnetic Resonance (NMR) which allows for different atomic aspects of the membrane to be seen. Combing this with computer models, we will be able to build a structure of the membrane which is atomically accurate. Understanding membranes is important for a variety of reasons. First they are present in all plants and animals and indeed are one of the reasons that life exists. Understanding the structure of membranes is also needed to understand the regulation of cell activity and so this research will have a major impact on our understanding of the mechanisms of transport across the cell membrane, such as drugs and nutrients. The results of the study will aid descriptions of many of the things that membranes do, such as signal transduction - which is important in passing messages between brain cells and the body via molecules called neurotransmitters, the passage of drugs into cells and the effect of external influences on cells from toxins and antimicrobial agents.

本工作的重点是观察组成细胞膜的分子之间的原子和分子相互作用。细胞膜是生命的守门人。生命已经从单细胞生物进化到更复杂的多细胞生物，部分原因是细胞膜的区室化。在上个世纪，最大的挑战之一是解码DNA -生命的分子蓝图。在下一个世纪，最大的挑战之一是了解膜是如何形成和发挥作用的;因为它们不仅无处不在，而且是维持生命所必需的。细胞膜控制着什么可以进出细胞，所谓的“分子交通”充当着守门人。这种作用对控制疾病、疾病和人体不同部位的营养平衡都很重要。这项研究建议在原子尺度上观察构成生物膜的分子之间的相互作用，在那里人们可以看到不同分子中的单个原子如何相互作用。这很重要，因为它揭示了交互的细节，并可以告诉我们这些交互是如何发生的。将用于观察膜的原子结构的技术是使用英国ISIS中子设施的中子散射技术，该设施位于牛津郡（英国）的卢瑟福阿普尔顿实验室，并由英国政府资助的科学和技术设施理事会理事会（STFC）管理。使用中子对这些分子的测量显示了存在的不同原子之间相互作用的细节。将使用的另一种技术是核磁共振（NMR），其允许看到膜的不同原子方面。将其与计算机模型相结合，我们将能够构建原子精确的膜结构。了解膜的重要性有多种原因。首先，它们存在于所有的植物和动物中，确实是生命存在的原因之一。了解膜的结构也需要了解细胞活性的调节，因此这项研究将对我们理解跨细胞膜的运输机制产生重大影响，例如药物和营养素。这项研究的结果将有助于描述膜所做的许多事情，例如信号转导-这对于通过称为神经递质的分子在脑细胞和身体之间传递信息非常重要，药物进入细胞以及毒素和抗菌剂对细胞的外部影响的影响。

项目成果

Alteration of water structure by peptide clusters revealed by neutron scattering in the small-angle region (below 1 Å(-1)).

小角度区域（低于 1 ×(-1)）的中子散射揭示了肽簇对水结构的改变。

• DOI: 10.1016/j.bpj.2012.08.010
• 发表时间: 2012
• 期刊: Biophysical journal
• 影响因子: 3.4
• 作者: Daidone I

On the hydration and conformation of cocaine in solution

• DOI: 10.1016/j.cplett.2017.03.040
• 发表时间: 2017-05-16
• 期刊: CHEMICAL PHYSICS LETTERS
• 影响因子: 2.8
• 作者: Gillams, Richard J.;Lorenz, Christian D.;McLain, Sylvia E.
• 通讯作者: McLain, Sylvia E.

Conformation and interactions of dopamine hydrochloride in solution.

溶液中盐酸多巴胺的构象和相互作用。

• DOI: 10.1063/1.4904291
• 发表时间: 2015
• 期刊: The Journal of chemical physics
• 作者: Callear SK

On the structure of water and chloride ion interactions with a peptide backbone in solution.

关于水和氯离子与溶液中肽主链相互作用的结构。

• DOI: 10.1039/c3cp53831a
• 发表时间: 2013
• 期刊: PCCP
• 作者: Busch S