Lipid-peptide interactions in cell membranes

Lead Research Organisation: University of Birmingham
Department Name: Sch of Biosciences

Abstract

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.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M01116X/1 01/10/2015 30/09/2023
1644236 Studentship BB/M01116X/1 05/10/2015 30/09/2019 Alexandra Martin
 
Description Cell membrane properties are influenced by composition. Lipids are a key component of cell membranes and the structure of the lipids present in different cell membranes determines physical properties such as fluidity and electrical barrier properties. We have observed that by modifying the charge of lipid headgroups and by systematically changing the composition of cell membrane models, the model membrane thickness and stability can be altered.
We have also characterised the effects of isotopically labelling lipids. Isotopic labelling is frequently used in different characterisation methods to label or hilight specific regions of interest, under the assumption that the labeling itself does not influence behaviour such as reactivity. We have observed that deuterium-substituted lipid tails changes the phase behaviour of lipids.
We have also begun to characterise the importance of lipid diversity between mammalian and bacterial cell membranes. Different anionic lipids are found in the cells of mammals and bacteria and our results suggest that models of bacterial cell membranes are more fluid and are poorer electrical barriers than models of mammalian cell membranes
Exploitation Route The aims of our research are to characterise cell membrane models and to understand the behaviour of membranes of different compositions. Our results will be of use to research using membrane models to support other membrane species such as membrane proteins or antibacterial peptides intended to interact with cell membranes. More biomimetic models will improve the validity of the models and will help better design drug candidates to target bacterial cell membranes.
Sectors Agriculture, Food and Drink,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology