Oxidative damage to lung surfactant and lipid membranes

Hemming, Joanna (2015) Oxidative damage to lung surfactant and lipid membranes. PhD thesis, Birkbeck, University of London.

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Abstract

Lung surfactant is a mixed monolayer of lipids and proteins that reduce the surface tension at the air-­‐lung interface to prevent alveolar collapse. Exposure of lung surfactant to ozone pollution has been linked to an increased risk of death due to respiratory diseases. This work aimed to determine the ozone damage caused to lung surfactant at the air-­‐water interface. A range of analytical techniques showed that peptide mimics of surfactant protein B were rapidly oxidised by ozone but no cleavage of the peptides occurred. Neutron reflectivity revealed that the peptides remained at the air-­‐water interface after oxidation but that their interaction with anionic phospholipids, thought to be crucial to their function, was significantly reduced. Neutron and X-­‐ray reflectivity experiments showed that exposure of different lipid monolayers to ozone led to a loss of unsaturated phospholipid material from the interface, whereas oxidised cholesterol remained but the molecules were considerably reorganised. The ozonolysis of whole animal lung surfactant was then investigated and it was shown that material was lost from the interface during reaction and that the monolayer was much less capable of reducing surface tension. Additionally, molecular dynamics simulations were performed, determining that surfactant protein C can significantly influence the ordering of surrounding phospholipids in a monolayer and that palmitoylation of the protein leads to an increase in this ordering effect. Finally, the uses of neutron scattering to explore the oxidation of lipid membranes were investigated. It was shown that neutron reflectivity of supported phospholipid bilayers at the solid-­‐ liquid interface is a useful tool for determining their reactivity with different reactive oxygen species. Small angle neutron scattering and off-­‐specular neutron reflectivity were also shown to be valuable methods for exploring the changes in lipid raft formation upon oxidation of phospholipids.

Item Type: Thesis (PhD)
Copyright Holders: The copyright of this thesis rests with the author, who asserts his/her right to be known as such according to the Copyright Designs and Patents Act 1988. No dealing with the thesis contrary to the copyright or moral rights of the author is permitted.
School/Department: School of Science > Biological Sciences
Depositing User: ORBIT Editor
Date Deposited: 12 Mar 2015 14:21
Last Modified: 04 Aug 2015 11:40
URI: http://bbktheses.da.ulcc.ac.uk/id/eprint/117

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