Chiral supramolecular architecture of stable transmembrane pores formed by an α-helical antibiotic peptide in the presence of lyso-lipids.

The amphipathic α-helical antimicrobial peptide MSI-103 (aka KIA21) can form stable transmembrane pores when the bilayer takes on a positive spontaneous curvature, e.g. by the addition of lyso-lipids. Solid-state P- and N-NMR demonstrated an enrichment of lyso-lipids in these toroidal wormholes. Anionic lyso-lipids provided additional stabilization by electrostatic interactions with the cationic peptides. The remaining lipid matrix did not affect the nature of the pore, as peptides maintained the same orientation independent of lipid charge, and a change in membrane thickness did not considerably affect their tilt angle. Under optimized conditions (i.e. in the presence of lyso-lipids and appropriate bilayer thickness), stable and well-aligned pores could be obtained for solid-state H-NMR analysis. These data revealed for the first time the complete 3D alignment of this representative amphiphilic peptide in fluid membranes, which is compatible with either monomeric helices as constituents, or left-handed supercoiled dimers as building blocks from which the overall toroidal wormhole is assembled.