Microcavity supported lipid bilayers; biomimetic models of the cell membrane

Biomimetic models of the cell membrane are sought after as they have the potential to provide a realistic representation of an organism’s lipid bilayer. They can be used to understand lipid dynamics, signalling, drug permeability and membrane protein diffusion in an environment that is away from the complexity of the real living cell. This thesis examines the application of a new type of lipid membrane model, the micro-cavity supported lipid bilayer (MSLB), to study drug-membrane interactions and glycolipid containing bilayers using electrochemical impedance spectroscopy (EIS). Chapter 1 outlines the structure and function of the cell membrane and describes current models used to replicate the functions of the cellular bilayer. The limits of these models are also discussed particularly in the context of stability, lipid fluidity and addressability of both sides of the bilayer. The biomimetic MSLB system is then explored as a viable alternative in this thesis and is described in Chapter 2. 2.80 ± 0.04 μm diameter gold arrays were used and their surfaces were chemically modified to render them hydrophilic which aided the assembly of lipid bilayers using Langmuir Blodgett to form the initial monolayer and vesicle disruption to create the final bilayer structure. This model is applied in Chapter 3 as a means of assessing drug plasma membrane interactions of two representative non-steroidal anti-inflammatory drugs; ibuprofen and diclofenac. These drugs were chosen as their log P values are well established and their interactions with membranes have been characterized by other methods. Their impact on the cavity array supported lipid membrane was investigated using EIS. Chapter 4 uses the MSLB model to study the interactions between the ganglioside, GM1, and disease relevant lectins by fabricating asymmetric GM1 containing lipid bilayer membranes. The influence of lipid/sterol composition on GM1-lectin recognition and aggregation was also considered. Overall, this work demonstrates that, using EIS as the interrogation method, it is possible to sensitively explore interactions between external molecules and the lipid bilayer using these MSLBs. The MSLBs are a significant advance on current lipid membrane models as they permit accurate representations of cell membrane in elements of composition, fluidity, asymmetry and deep aqueous well on either side of the membrane