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Title: Model membrane structure and morphology studied by atomic force microscopy
Author: Parsons, Edward Stephan
ISNI:       0000 0004 7656 9965
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2016
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The plasma membrane is comprised of a complex mixture of lipids and proteins that most simply acts to compartmentalise the cells interior from its external environment. The structure of the membrane adopts that of the lipid bilayer motif that acts as a supporting matrix in which integral and peripheral membrane proteins can diffuse. This results in a heterogeneous and dynamic environment that has a direct impact upon biomolecular function. An understanding such a complex system is often sought through minimal models that mimic the behaviour(s) of the native membrane but with a greatly reduced number of molecular components. Despite their relative simplicity, they can yield an insight in to the key driving forces of specific membrane processes. This thesis is concerned with the study of the structure and morphology adopted by model membrane systems, with atomic force microscopy providing a nanoscale view of the given membranes surface. Four distinct systems are studied: (i) By constructing phase-separated supported lipid bilayers with a systematic height mismatch between domains, it is demonstrated how height mismatch increases line tension, and drives the formation of smaller, more circular domains. (i) The sphingomyelin ripple phase is shown to be disrupted by cholesterol and ceramide dopants via two very different mechanisms, with cholesterol 'melting' the gel-like regions with little increase in ripple periodicity, whilst ceramide adds to the gel and elongates the periodicity. (iii) Thin films of inverse lipid phases are prepared and visualized, with the terminating lattice observable for the bicontinuous cubic phase of pure monoolein, although imaging of other inverse lattices remains elusive. (iv) It is shown that cholesterol is not required for collapse of the intermedilysin pre-pore complex prior to perforation, thus uncovering this collapse as a distinct mechanistic step. Each of these systems studied demonstrate the power of model systems in revealing the physicochemical behaviour that underpins membrane processes.
Supervisor: Seddon, John ; Luckham, Paul ; Saffell, Jane Sponsor: Engineering and Physical Sciences Research Council ; Biotechnology and Biological Sciences Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral