Tuning Membrane Asymmetry

Abstract

The basic building block of any organism is the cell, a self-contained unit enveloped by a semi-permeable plasma membrane. This small structural unit in turn is further compartmentalised in eukaryotic organisms, containing several organelles many of whom possess their own membranes. The classic Singer-Nicholson model presented the structure of these membranes as fluid assemblies of lipids, in a bilayer functionally. Whilst a landmark contribution in the field of lipidomics, the model omitted a key feature of the membrane, asymmetry. Bilayers are found to be transversely asymmetrical, with anionic lipids dominating the inner, cytosolic leaflet, whilst zwitterionic and sphingophospholipids are predominately found in the extra-cellular leaflet.Classically, membranes mimics employed in-vitro have largely been transversely symmetric with the exception of supported lipid bilayers, which allow greater control of the composition of each leaflet. However issues with support interaction, impairing features of the bilayer, affecting membrane insertion and diffusion rates of bilayer components both laterally and transversely. Only in the past decade have asymmetric bilayer synthetic methodologies began to emerge, including, droplet interface bilayers, inverted emulsion techniques and methyl-β-cyclodextrin catalysed exchange. Each technology is in its infancy, with limitations on the properties of the bilayers, as well as their applications. The latter method is the only method capable of forming asymmetric liposomes in a broad range of diameters. A new methodology to produce transversely asymmetric liposomes will be presented utilising synthetic lipids capable of molecular recognition.