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Molecular Simulations of Model Bilayers of Skin Lipids
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O'Neill, D. W. (2019) Molecular Simulations of Model Bilayers of Skin Lipids. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b3439469~S15
Abstract
The lipid matrix within the SC is believed to be the main contributor to the skin's barrier properties. But the major problem is that the organisation of the lipids into the lamellar layers and their contribution to the barrier properties of the skin remains poorly understood. This thesis has attempted to address this issue through the use of molecular simulations of model bilayers of the SC under a variety of different conditions. The use of molecular dynamics simulations has allowed these membranes to be studied at the atomistic level that isn't accessible through conventional experiments.
It is shown that the hydration level within the lipid matrix has a direct impact on the bilayer conformation and thus the barrier properties of the SC. At low hydration a pooling effect is observed on the bilayer surface, which affects the order and orientation of the CERs. Lowering the hydration reduces the amount of CER-water hydrogen bonds and replaces them with adjacent CER-CER hydrogen bonds. The lateral hydrogen bonding network remains unchanged.
Through free energy calculations and the calculation of permeability coefficients, a mixed system of CER and OA has a greater permeability than either of its pure counterparts and thus would be a more favourable pathway for permeants, such as water, to migrate through. This enhanced permeability is shown to be due a combination of weakening the lateral hydrogen bonding network and disrupting the packing with it's 'kinked' tail.
Finite size and solvent effects on CG simulations with the interaction of DMSO on CER bilayers are presented. At low solvent to lipid ratios and larger bilayers, the small solvent chamber allows interactions of the CER bilayer with it's periodic image causing disruption to the conformation and leading to a change to a hexagonal phase. Solvent effects are observed when the amount of DMSO at the interface is higher for larger bilayer systems despite the same solvent to lipid ratio as a larger surface area can accommodate a greater number of DMSO molecules at the interface. Our results suggest that the system sizes of at least 256 lipids and 30 solvent molecules per lipid are required to avoid finite size effects in simulations of lipid membranes in mixed solvents.
Item Type: | Thesis (PhD) | ||||
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Subjects: | Q Science > Q Science (General) T Technology > T Technology (General) |
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Library of Congress Subject Headings (LCSH): | Molecular microbiology, Lipids, Skin, Simulation methods | ||||
Official Date: | July 2019 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | Department of Chemistry | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Notman, Rebecca | ||||
Sponsors: | Engineering and Physical Sciences Research Council | ||||
Format of File: | |||||
Extent: | xiv, 143 leaves: illustrations, charts | ||||
Language: | eng |
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