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Lipid-peptide interactions in cell membranes

细胞膜中的脂质-肽相互作用

基本信息

批准号：
1644236
负责人：
金额：
--
依托单位：
University of Birmingham
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2015
资助国家：
英国
起止时间：
2015 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-1644236
关键词：
Lipid peptide interactions cell membranes

项目摘要

Knowledge of the interaction of membrane peptides with the lipids comprising the membrane is crucial to understanding both the mechanism by which they enter the membrane and their function. The membrane composition plays an important role in its interaction with a peptide; for example, some proteins interact specifically with particular lipid headgroups. This project will probe the interaction of antimicrobial peptides and bacterial membrane proteins with model cell membranes formed from bilayers of various phospholipids, sphingolipids and cholesterol, designed to mimic mammalian and bacterial cell membranes.This project will employ a range of physical probes, including spectroscopic, imaging and reflectometry methods. Penetration of the bilayer by a peptide can be followed with electrochemical measurements and an electric field can also be applied across an electrode-supported bilayer to mimic the effects of potential gradients and charge asymmetry across the membrane. The physical probes employed can all be carried out in the presence of the applied field to determine its effect on membrane organisation. Focus will be on the effect of composition on peptide incorporation with a view to understanding how and why peptides interact selectively with bacterial or mammalian cell membranes. This will develop a molecular-level understanding of the interactions and the knowledge generated will further understanding of the reasons behind the selectivity and better predict or design peptides with potential application as therapeutic agents.

了解膜肽与构成膜的脂类的相互作用对于了解它们进入膜的机制和它们的功能都是至关重要的。膜的组成在其与肽的相互作用中起着重要的作用；例如，一些蛋白质与特定的脂头基团特异地相互作用。该项目将探索抗菌肽和细菌膜蛋白与由不同磷脂、鞘脂和胆固醇双层形成的模拟细胞膜的相互作用，旨在模拟哺乳动物和细菌细胞膜。该项目将使用一系列物理探测器，包括光谱、成像和反射测量方法。在多肽穿透双层膜之后，可以进行电化学测量，还可以在电极支撑的双层膜上施加电场，以模拟跨膜的电位梯度和电荷不对称的影响。所使用的物理探针都可以在外加电场的情况下进行，以确定其对膜组织的影响。重点将放在组成对多肽结合的影响上，以期了解多肽如何以及为什么选择性地与细菌或哺乳动物细胞膜相互作用。这将发展对相互作用的分子水平的理解，所产生的知识将进一步了解选择性背后的原因，并更好地预测或设计具有潜在治疗应用的多肽。