Publication I April 28, 2022
Highly shape- and size-tunable membrane nanopores made with DNA
Membrane nanopores are key for molecular transport in biology, portable DNA sequencing1,2,3,4, label-free single-molecule analysis5,6,7,8,9,10,11,12,13,14 and nanomedicine5. Transport traditionally relies on barrel-like channels of a few nanometres width, but there is considerable scientific and technological interest for much wider structures of tunable shape. Yet, these nanopores do not exist in nature and are challenging to build using existing de novo routes for proteins10,15,16,17. Here, we show that rational design with DNA can drastically expand the structural and functional range of membrane nanopores. Our design strategy bundles DNA duplexes into pore subunits that modularly arrange to form tunable pore shapes and lumen widths of up to tens of nanometres. Functional units for recognition or signalling can be optionally attached. By dialling in essential parameters, we demonstrate the utility and potential of the custom-engineered nanopores by electrical direct single-molecule sensing of 10-nm-sized proteins using widely used research and hand-held analysis devices. The designer nanopores illustrate how DNA nanotechnology can deliver functional biomolecular structures to be used in synthetic biology, single-molecule enzymology and biophysical analysis, as well as portable diagnostics and environmental screening.