Unimolecular Transmembrane Na+ Channels Constructed by Pore-Forming Helical Polymers with a 2.3 Å Aperture

Abstract

To understand the relationships between channel size and ion selectivity, we have developed a new type of artificial ion channel based on pore-forming helical polymers consisting of phenanthroline-oxadiazole units with a pore aperture 2.3 Å close to the diameter of the Na+ ion (2.04 Å). Successful preparation of high molecular weight helical polymers (HP1) gives rise to a 4.6 nm long artificial unimolecular transmembrane channel. The transport property of artificial channel HP1 was elaborately investigated by means of vesicle-based kinetic assay and symmetry/asymmetry bilayer membrane (BLM) experiments as well. These results unambiguously demonstrate that HP1 is a Na+-selective channel with extremely high transport activity (EC50 = 0.017 mol % relative to lipid). Moreover, the Na+/K+ selectivity ratio of HP1 reaches 1.9, as determined by asymmetry BLM experiments. Owing to the narrowest 2.3 Å size constraint so far, HP1 transport naked Na+ ion across the membrane, which represents a different Na+ transport mode from that of natural Na+ channels, which transports partially hydrated Na+ ions during transmembrane conduction. This study provides crucial insights on the chemical basis of ion selectivity in the field of ion channels.