Understanding the electrochemical interaction between the hybrid bilayer lipid membranes and amyloid‐β

Abstract

AbstractBackgroundBiomimetic membrane systems can be deposited onto conductive metal surfaces to study the physical properties of membranes as well as the behaviour of proteins within these membranes using electrochemical and surface analytical techniques [1]. Although there are several types of biomimetic membrane, hybrid bilayer lipid membranes (HBLMs) have attracted wide interest. Traditionally, HBLMs have been developed by electrodepositing alkanethiol self‐assembled monolayers onto gold surfaces, which can then be further modified by depositing a secondary phospholipid layer to form the HBLM. Although HBLMs have been widely regarded due to them being robust, relatively straightforward to make, as well as being easy to modify according to the users needs, several concerns surround HBLMs including their reduced fluidity compared to true cell membranes. This is due to the alkanethiol layer being crystalline in nature and more densely packed, resulting in difficulty to reconstitute transmembrane proteins within them.MethodScreen‐printed carbon electrodes are modified with diazonium based phenyl alkyl groups using different protocols to evaluate the biomimetic differences of these novel HBLMs. 2,2‐diphenyl‐1‐picrylhydrazyl is used to prevent the formation of polyaryl layers on the surface of the electrode, hence limiting the electrodeposition to a monolayer. The HBLMs are formed by depositing the second layer in the form of dihexadecyl phosphate, which are analyzed using differential pulse voltammetry, ellipsometry, and X‐ray photoelectron spectroscopy.ResultThe different HBLMs presented are embedded with amyloid‐β1‐42 (Aβ42), the hallmark protein implicated in Alzheimer’s Disease, to assess the protein‐membrane interactions using HBLMs. Aβ42 is known to aggregate to form dimers, oligomers, fibrils, and plaques. Hence using electrochemical techniques, we are able to monitor the aggregation of Aβ42 in the HBLMs. The aggregation process was accelerated by the presence of the bilayer membrane.ConclusionThe electrochemical platform presented here enables us to understand how the interaction of amyloid‐β with the bilayer membrane can alter the aggregation pathways and also affect the formation of toxic oligomer species.