Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.506020
Title: Solid-state NMR and x-ray diffraction investigations of sphingomyelin model membranes
Author: Shaw, Karen Paula
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2009
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Abstract:
The only sphingolipid occurring naturally in mammalian cells, sphingomyelin (SM) is of great importance. Having predominantly long, saturated acyl chains it has an unusually high melting temperature (around physiological temperature) and has been strongly associated with lipid microdomains often referred to as 'lipid rafts'. These domains are proposed to be enriched in SM and cholesterol (Chol) and have been linked to many cell processes and disease states. Despite the important role SM plays in the cell membrane, there is relatively little published data available in the literature. The first chapter of this work investigates the behaviour of SM from three natural sources, bovine brain (BBSM), egg yolk (EYSM) and milk (MSM). This allows a comparison of the phase behaviour in terms of the different chain compositions in each extract. The results show that the extracts differ in their gel phase structures and we present the first x-ray diffraction data for a ripple phase (Pβ') in BBSM and EYSM. At sufficiently high concentrations, Chol acts to disrupt the gel phase (Lβ) and order the fluid phase (Lα) of SM, leading to the formation of the 'intermediate' liquid ordered (Lo) phase. This phase retains characteristics of both the Lβ and Lα phases and has been strongly associated with lipid rafts. Using a combination of x-ray diffraction and ³¹P solid-state NMR, we have investigated the disruption of the gel phase of BBSM at low Chol concentrations. The results show disruption of the regular packing of the gel phase and also the removal of the ripple phase at 15mol% Chol. Finally, time-resolved x-ray diffraction techniques were utilised to investigate the kinetics of the different lamellar transitions observed. The Lβ to Lα and the Pβ' to Lα transitions are compared in MSM and BBSM.
Supervisor: Law, Robert ; Seddon, John Sponsor: EPSRC ; ESRF
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.506020  DOI: Not available
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