Studies of lipid bilayers incorporating a peptide or small molecule

• Main Author: Cudmore, Andrew James Anderson
• Published: University of Edinburgh 1995
• Subjects: 572
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648990

Synthetic phospholipid membrane structures have been studied, primarily by X-ray diffraction and the swelling series phase assignment method. The first part of this thesis describes a study of the interaction of a small lipophilic molecule in two different charge forms, amantadine free base and hydrochloride, with fluid phase dioleoylphosphatidylcholine (DOPC) bilayers. Although diffraction data were collected out to eight orders from these bilayers, the swelling series method could only phase the first five orders of diffraction. Measurement of the meridional diffraction spacing showed that the DOPC bilayer thickness decreased by 1 to 2.5Å on addition of either charge form of amantadine. Little more could be deduced about the interaction of amantadine with DOPC bilayers, because of the limited ability of the swelling series method to phase the diffraction data. The second part of this thesis describes the study of a brominated phospholipid, which might provide an alternative to the swelling series phasing method. The synthetic brominated phospholipid is an analogue of dipalmitoyl-phosphatidylcholine (DPPC), where the terminal methyl group of the <I>sn</I>-2 chain has been exchanged for a bromine atom. This bromine atom 'label' has been incorporated into a phospholipid by substitution for a group of similar atomic radius, 1.85Å versus 2.00Å, thus creating a molecule which is sterically similar to its unlabelled analogue. The bromolipid and DPPC were studied independently, in both the gel (L<SUB>β'</SUB>) and fluid (L<SUB>α</SUB>) phase, and as mixtures, solely in the gel (L<SUB>β'</SUB>) phase. Comparison of the gel and fluid phase electron density maps showed that the major difference between the DPPC and bromolipid bilayers was the presence of an electron dense region at the centre of the bromolipid lipid layer.