Screening the Insertion of Families of Bioactive Microbial Metabolites into Tethered Bilayer Lipid Membranes (TBLMS)

Abstract

While it is known that many microbial metabolites can permeabilize phospholipid membranes, it is not easy to find quantitative comparisons across large numbers of such metabolites. Such comparisons are of use in screening likely candidates for ongoing research into the development of new and improved antibiotics. We have studied the effects of 30 microbial metabolites on the electrical conductivity of a tethered bilayer lipid membrane comprising two standard phospholipid components. The technique allows rapid quantification of the activity of these compounds. As well as the electrical conductivity, we have analyzed the changes in membrane capacitance by the insertion of metabolites which reports on the change of membrane thickness, as well as the introduction of water molecules into the membrane. Using a standard 10 µM concentration for each of the 30 metabolites, we rank them according to their impact on membrane conduction in PBS solution (Fig 1). We also demonstrate that by determining the change in conduction (ΔG) against the change in capacitance (ΔC) caused by membrane insertion it is possible to determine the complexation properties of the metabolites as they insert into the membrane.View Large Image | View Hi-Res Image | Download PowerPoint Slide