The main focus of this thesis is on the effects caused by α-helical peptides on liposome structure, the impact of cholesterol on the peptide-membrane interactions, and the effect of aggregate curvature on the peptide affinity. Results of the studies show that the membrane destabilizing effect of the cationic α-helical peptide melittin is modulated by cholesterol. Melittin induces leakage from pure phospholipid liposomes in a manner that is compatible with the presence of small pores. In the case of cholesterol-supplemented liposomes leakage coincides, however, with major structural transformations and rupture of the liposomes. Cholesterol decreases the affinity of melittin for phospholipid bilayers, but once the peptide has adsorbed to the membrane the presence of cholesterol does not offer any resistance against melittin-induced membrane destabilization. Our investigations indicate that cholesterol affects the alamethicin-lipid bilayer interactions in a similar way. PEG-stabilized bilayer disks are formed upon addition of polyethylene glycol (PEG)-lipids to lipid mixtures with high bending rigidity. The partial segregation of components within the bilayer disk, suggested by theoretical calculations and experimental observations, was verified by small angle neutron scattering. By means of a novel competitive binding assay it was shown that the three α-helical peptides melittin, alamethicin, and magainin have high affinity for the curved rim of PEG-stabilized bilayer disks. The bilayer disks have structural, and other properties, that make them interesting for the formulation of peptides and membrane-associated proteins. For stability reasons dry formulations are often preferred. The PEG-stabilized bilayer disks were shown to retain their structure in rehydrated samples that had been freeze- or spray-dried in the presence of lactose.
| Identifer | oai:union.ndltd.org:UPSALLA1/oai:DiVA.org:uu-89432 |
| Date | January 2009 |
| Creators | Wessman, Per |
| Publisher | Uppsala universitet, Fysikalisk kemi, Uppsala : Acta Universitatis Upsaliensis |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Doctoral thesis, comprehensive summary, info:eu-repo/semantics/doctoralThesis, text |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, 1651-6214 ; 610 |
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