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Continuous observation of the stochastic motion of an individual small-molecule walker

Nature Nanotechnology volume 10, pages 76–83 (2015)Cite this article

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Abstract

Motion—whether it the ability to change shape, rotate or translate—is an important potential asset for functional nanostructures. For translational motion, a variety of DNA-based and small-molecule walkers have been created, but observing the translational motion of individual molecules in real time remains a significant challenge. Here, we show that the movement of a small-molecule walker along a five-foothold track can be monitored continuously within a protein nanoreactor. The walker is an organoarsenic(III) molecule with exchangeable thiol ligands, and the track a line of cysteine residues 6 Å apart within an α-haemolysin protein pore that acts as the nanoreactor. Changes in the flow of ionic current through the pore reflect the individual steps of a single walker, which require the making and breaking of As–S bonds, and occur in aqueous solution at neutral pH and room temperature. The walker moves considerably faster (∼0.7 s per step) than previous walkers based on covalent chemistry and is weakly processive (6 ± 1 steps per outing). It shows weak net directional movement, which can be described by a thermodynamic sink arising from the different environments of the cysteines that constitute the track.

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Figure 1: The walker and its track.
Figure 2: Electrical recordings of αHL pores containing a single-Cys residue in the presence of SPAA–MEET2.
Figure 3: Comparison of the reaction of SPAA–MEET2 with single-Cys and double-Cys mutant αHL pores.
Figure 4: Electrical recordings of αHL pores containing double-Cys mutations in the presence of SPAA–MEET2.
Figure 5: Electrical recordings of an αHL pore containing a triple-Cys mutation in the presence of SPAA–MEET2.
Figure 6: Electrical recordings of the αHL pore containing a five-Cys track in the presence of SPAA–MEET2.

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Acknowledgements

This work was supported by an European Research Council Advanced Grant. G.S.P. was supported by an International Incoming Fellow–Marie Curie Actions Grant. L-S. Choi was the recipient of a University of Oxford Croucher Scholarship (UOCS). The authors thank I. Leung for his guidance with NMR measurements.

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Authors and Affiliations

  1. Department of Chemistry, University of Oxford, Oxford OX1, 3TA, UK

    Gökçe Su Pulcu, Ellina Mikhailova, Lai-Sheung Choi & Hagan Bayley

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  1. Gökçe Su Pulcu
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  2. Ellina Mikhailova
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Contributions

G.S.P. designed and performed experiments, analysed data and wrote the paper. E.M. prepared the protein samples. L.C. synthesized the molecular walker and performed experiments. H.B. designed experiments, analysed data and wrote the paper.

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Correspondence to Gökçe Su Pulcu or Hagan Bayley.

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The authors declare no competing financial interests.

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Pulcu, G., Mikhailova, E., Choi, LS. et al. Continuous observation of the stochastic motion of an individual small-molecule walker. Nature Nanotech 10, 76–83 (2015). https://doi.org/10.1038/nnano.2014.264

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