Interactions of an antimicrobial reptaibol with amphiphilic block copolymers

Abstract

In this thesis the behavior of binary membranes from amphiphilic PMOXA-PDMSPMOXA triblock copolymers and the peptaibol alamethicin, an antimicrobial peptide, was investigated in the context of formation of novel biocomposite nanostructured materials. This task was achieved by employing monolayer and bilayer systems. Pure systems as well as mixtures of the individual materials were considered. The properties of mixed monolayers were studied by surface pressure-area isotherms and Brewster angle microscopy. Both pure and binary systems exhibit a rich phase behavior. As reported previously, functionality of alamethicin relies on its aggregation properties in lipid membranes. This is also the case in polymer matrices; however, here the mixing properties differ from lipid-peptide systems due to the polymers’ structural specificity. The peptide influence on the polymer films is provided in detail, and supported by the compressibility data to asses the elastic properties of such composite membranes. Surface topography of deposited Langmuir-Blodgett films was analyzed by scanning force microscopy to foster the conclusions drawn from results obtained for the air-water interface. Although natural membrane proteins are optimized for lipid bilayers, our results suggest that block copolymers membranes may provide a better environment for the peptide. The pore forming behavior of alamethicin in vesicular systems built from amphiphilic block copolymers was further investigated by transmission electron microscopy and dynamic light scattering. A significant increase in cation permeability was assigned to the intrinsic ion transport activity of alamethicin and therefore a functional reconstitution of the peptide in self-assembled membranes built from synthetic block copolymers could be proven. This thesis is structured into seven chapters. In the introductory chapter the basic idea and the goals of this work are elucidated. Chapter two provides the theoretical background explaining the molecular interactions at the air-water interface subsequently pursued by insights into the amphiphilic and self-assembly behavior of phospholipids and block copolymers as well as the functionalization of natural and synthetic membranes by integration of membrane proteins. In chapter three the experimental conditions are revealed followed by chapter four in which the obtained results are discussed in depth. The conclusions which were drawn as well as an outlook for prospective investigations are given in chapter five. The thesis is finalized by the list of literature references and an appendix.