Mimicking Microbial Membranes

Author: Jakob Andersson

Andersson, Jakob, 2018 Mimicking Microbial Membranes, Flinders University, College of Science and Engineering

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Model membranes provide a controlled environment in which biophysical studies of membrane processes and membrane proteins can be carried out. This is necessary as the cell membrane is a highly complex structure which makes systematic studies of its individual components very challenging. Tethered bilayer lipid membranes provide a stable self-assembled membrane platform that can be studied a wide range of analytical tools, but the range of studies that can be carried out is limited by the number of architectures that are currently available. A number of new tether architectures were designed in this project to better facilitate the study of membrane proteins and ion transport across lipid bilayers.

Chapter 3 presents the use of a well-established tethered membrane architecture to study the ability of novel crown ether compounds to selectively transport ions across a lipid membrane without damaging the membrane itself. Chapter 4 presents novel anchorlipids to increase the range of available membrane architectures. It examines the effect that chemical modifications to the anchorlipid molecule have on the electrical and structural properties of the membrane.

Based on the development of these novel architectures, a new type of self-assembled membrane was developed mimicking the outer membrane of Gram-negative bacteria, which is presented in chapter 5. This enabled for the first time the study of this membrane type by electrochemical impedance spectroscopy, and significantly simplifed the assembly process of the membrane for other studies such as neutron scattering.

The new model membrane was used to study the effects of membrane-targeting antibiotics as well as the effect of gold nanoparticles on the electrical properties of the lipid bilayer. The development of this membrane architecture will enable a wide range of future studies to further investigate the effect of membrane-targeting antibiotics as well as providing a new avenue of approach to design novel membrane-targeting antibiotics to meet the increasingly urgent need for new antibiotics to combat the threat of multi-drug resistant bacteria.

Chapter 6 uses the membrane architectures developed in chapter 5 to investigate novel approaches to target the outer membrane of gram-negative bacteria using a combination of an antibiotic and a nanomaterial. Finally, in chapter 7 an outlook is presented for future developments based on the work presented in this thesis.

Keywords: Drug Resistant Bacteria, Gram-negative Bacteria, Model Membranes, Outer Membrane, Antibiotics

Subject: Chemistry thesis

Thesis type: Doctor of Philosophy
Completed: 2018
School: College of Science and Engineering
Supervisor: Associate Professor Ingo Koeper