The interaction of proteins with membranes is central to numerous cellular processes, playing a major role in human amyloid disease states such as Parkinson's disease. Membrane bound receptors also play a vital function in cell signalling, and are thus a target for many drugs. However, the analysis of these interactions in their native environments with their subsequent ligands pose problems due to the technical difficulty in depositing membranes for analysis by conventional techniques such as surface plasmon resonance (SPR).

The aim of this research is to develop a technique based on the optical method of total internal reflection ellipsometry (TIRE) for the analysis of protein interactions at native cellular membranes. TIRE is a combination of spectroscopic ellipsometry and SPR that offers 10-times better sensitivity in the detection of binding between a ligand and its receptor compared to SPR alone, and TIRE enables the use of natively derived membranes as opposed to synthetic lipid environments, via Langmuir-Schaefer deposition. Critically, we have been able to observe interactions at native membranes using whole cells and isolated organelles in which the receptors and lipid surfaces remain largely intact.

We have applied this technology to the analysis of two distinct types of biological processes: protein:receptor interactions involving chaperone-mediated post-translational protein targeting and membrane receptors; and protein:lipid interactions via amyloid oligomer interactions with natively derived membranes. These soluble oligomers and fibrils are known to interact directly with membranes and their interactions have been observed utilising whole cell membranes. This supports recent observations which indicate that both cell death and the spread of pathology occurs due to protein lipid interactions. Thus, we have been able to develop the TIRE methods to allow characterisation of protein:lipid and protein:receptor interactions in the context of native membranes.