Functional activity of peptide ion channels in tethered bilayer lipid membranes: Review

Ion transport across biomembranes plays a major role in living cells. This fundamental function is normally carried out by molecules with both a hydrophobic and a hydrophilic side (amphiphilic molecules), which aggregate within the membrane forming a hydrophilic pore (the ion channel) permitting the selective translocation of permeant ions. Countless papers report the conformation of these ion channels in lipid vesicles using several techniques, such as circular dichroism and solid-state NMR spectroscopies. However, the functional activity of ion channels can only be investigated by varying the transmembrane potential. This is also the situation in which ion channels operate in commercialized drugs with intracellular targeting activities, of great interest in pharmaceutical research. A suitable biomimetic membrane must consist of a conducting or semiconducting support, whose “heart” is a lipid bilayer in contact with the aqueous solution of interest on one side. The other side must comprise a hydrophilic region thick enough to completely decouple the lipid bilayer from the support, giving rise to a “tethered bilayer lipid membrane” (tBLM). This review aims to describe the numerous efforts made over time to approach this goal, the most recent achievements, and the perspectives of future development. Special emphasis will be placed on the electrochemical aspects of tBLMs, and a qualitative overview of the main optical and scanning probe techniques employed will be provided.