Intracellular neuronal recordings across DNA tiles

Transmembrane ionic flow through artificial ion channels is integral to the development of biohybrid electronics, such as neural interface technologies. However, achieving accurate and stable intracellular access through these synthetic analogues has remained a challenge. Here we use DNA origami tiles (0.8 nm diameter), anchored into live neuronal membranes, both with and without cholesterol tags, to demonstrate highly stable ion transport (net ~2 nS), channel-like stochasticity and intracellular drug delivery without disrupting neuronal physiology. These results are supported by molecular dynamics simulations. Using a suite of patch-clamp techniques, including two-photon-targeted variants, we obtain repeatable intracellular and quasi-intracellular voltage measurements across DNA tiles, eliminating the need for membrane break-in even from thin dendritic structures (~1 µm), which are inaccessible with standard electrodes. This advancement establishes an ‘outside looking in’ method to probe intracellular voltage dynamics using DNA nanostructure-based transmembrane access. Self-inserting DNA origami tiles form stable nanopores across live neuronal membranes, enabling intracellular-like voltage recordings, small-molecule delivery and access to hard-to-reach dendrites without membrane rupture.