Synthetic Lipid Membrane Channels Formed by Designed DNA Nanostructures

TLDR

We engineered nanometer‑scale transmembrane channels in lipid bilayers by self‑assembling DNA origami that form a membrane‑spanning stem and a cholesterol‑decorated barrel cap. Electrophysiology revealed ~1 nS conductance and gating akin to natural ion channels, with enhanced gating upon stem‑strand mutations, and single‑molecule translocation experiments demonstrated the channels can discriminate individual DNA molecules.

Abstract

We created nanometer-scale transmembrane channels in lipid bilayers by means of self-assembled DNA-based nanostructures. Scaffolded DNA origami was used to create a stem that penetrated and spanned a lipid membrane, as well as a barrel-shaped cap that adhered to the membrane, in part via 26 cholesterol moieties. In single-channel electrophysiological measurements, we found similarities to the response of natural ion channels, such as conductances on the order of 1 nanosiemens and channel gating. More pronounced gating was seen for mutations in which a single DNA strand of the stem protruded into the channel. Single-molecule translocation experiments show that the synthetic channels can be used to discriminate single DNA molecules.