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  5. The effect of the antioxidant alpha-tocopherol on the structure of phospholipid model membranes and lipid phase behaviour
 
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The effect of the antioxidant alpha-tocopherol on the structure of phospholipid model membranes and lipid phase behaviour
File(s)
Malia-D-2022-PhD-Thesis.pdf (6 MB)
Thesis
Author(s)
Malia, Divya
Type
Thesis or dissertation
Abstract
α-Tocopherol (vitamin E) is a powerful antioxidant within living cell membranes and whilst its antioxidant activity is well studied, its impact on lipids and lipid phase behaviour is less known. This work aims to elucidate how α-Tocopherol’s antioxidant function is enhanced at low concentrations within living cell membranes, and how its function could be best harnessed in increasing the shelf life of food products. The interaction of α-Tocopherol with phosphatidycholine model membranes has been analysed using X-ray diffraction, solid-state NMR, differential scanning calorimetry and microscopy techniques.
Our work has found that α-Tocopherol behaves similarly to cholesterol in that it promotes fluidisation in parts of the membrane and rigidity in other parts. We show phase separation in giant unilamellar vesicles comprised of ternary mixtures of dipalmitylphosphatidylcholine, dioleoylphosphatdiylcholine and α-Tocopherol using fluorescence microscopy. This is a novel finding as prior to this, phase separation has only been associated to sterols or stanols. The implications of this are wide ranging, as in vivo it is likely α-Tocopherol is forming a liquid ordered type phase. From commercial perspective, replacing cholesterol with α-Tocopherol would be a healthier alternative.
We have also reported the curvature inducing impact of α-Tocopherol in unsaturated phosphatidylcholines. X-ray diffraction data shows that α-Tocopherol induces an inverse hexagonal phase, which coexists with an Im3m inverse bicontinuous cubic phase at specific concentrations with dioleoylphosphatdiylcholine. We also report the formation of the hexagonal close packed phase which previously has only been reported once. This phase forms at certain compositions of α-Tocopherol, triolein (oil) and dioleylphosphatidylethanolamine. The formation of these curved structures demonstrates α-Tocopherol’s ability to minimise the water-oil interface as that is where oxidation reactions occur. Cubic phases are also extremely valuable for nutrient and drug delivery.
Version
Open Access
Date Issued
2022-06
Date Awarded
2022-11
URI
http://hdl.handle.net/10044/1/109512
DOI
https://doi.org/10.25560/109512
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
https://creativecommons.org/licenses/by-nc/4.0/
Advisor
Seddon, John
Law, Robert
Brooks, Nicholas
Sponsor
Nestlé
UK Research and Innovation
Grant Number
EP/R512540/1
Publisher Department
Chemistry
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)
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