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A biomimetic DNA-based channel for the ligand-controlled transport of charged molecular cargo across a biological membrane

Abstract

Biological ion channels are molecular gatekeepers that control transport across cell membranes. Recreating the functional principle of such systems and extending it beyond physiological ionic cargo is both scientifically exciting and technologically relevant to sensing or drug release1,2. However, fabricating synthetic channels1,3 with a predictable structure remains a significant challenge. Here, we use DNA as a building material4,5,6,7,8 to create an atomistically determined molecular valve that can control when and which cargo is transported across a bilayer. The valve, which is made from seven concatenated DNA strands, can bind a specific ligand and, in response, undergo a nanomechanical change to open up the membrane-spanning channel. It is also able to distinguish with high selectivity the transport of small organic molecules that differ by the presence of a positively or negatively charged group. The DNA device could be used for controlled drug release and the building of synthetic cell-like or logic ionic networks9,10.

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Figure 1: A rationally designed DNA nanopore features a nanomechanical and sequence-specific gate to regulate transmembrane flux.
Figure 2: Nanopore NP is of the expected dimensions and spans a lipid bilayer, thereby confirming the validity of the novel pore design.
Figure 3: A DNA key leads to the triggered opening of NP-C to yield NP-O, and both pores have distinct and expected molecular properties.
Figure 4: NP-C can control the DNA-triggered and charge-selective release of small-molecule cargo from a reservoir.

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Acknowledgements

This research was funded by the Leverhulme Trust (RPG-170), UCL Chemistry and the BBSRC (grant ref. BB/M012700/1). The authors thank A. Pyne and B. Hoogenboom from the London Centre for Nanotechnology for assistance with the AFM analysis of DNA nanopores, and H. Martin in aiding J.B. to render the images of the pores.

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J.B. and S.H. designed the DNA nanopores. J.B. carried out all experiments except nanopore recordings, which were conducted by A.S. N.F. co-supervised A.S. S.H. conceived the project, supervised J.B. and A.S., and wrote the manuscript with data input from J.B. and A.S.

Corresponding author

Correspondence to Stefan Howorka.

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The authors declare no competing financial interests.

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Burns, J., Seifert, A., Fertig, N. et al. A biomimetic DNA-based channel for the ligand-controlled transport of charged molecular cargo across a biological membrane. Nature Nanotech 11, 152–156 (2016). https://doi.org/10.1038/nnano.2015.279

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