Stepwise growth of surface-grafted DNA nanotubes visualized at the single-molecule level


DNA nanotubes offer a high aspect ratio and rigidity, attractive attributes for the controlled assembly of hierarchically complex linear arrays. It is highly desirable to control the positioning of rungs along the backbone of the nanotubes, minimize the polydispersity in their manufacture and reduce the building costs. We report here a solid-phase synthesis methodology in which, through a cyclic scheme starting from a ‘foundation rung’ specifically bound to the surface, distinct rungs can be incorporated in a predetermined manner. Each rung is orthogonally addressable. Using fluorescently tagged rungs, single-molecule fluorescence studies demonstrated the robustness and structural fidelity of the constructs and confirmed the incorporation of the rungs in quantitative yield (>95%) at each step of the cycle. Prototype structures that consisted of up to 20 repeat units, about 450 nm in contour length, were constructed. Combined, the solid-phase synthesis strategy described and its visualization through single-molecule spectroscopy show good promise for the production of custom-made DNA nanotubes.

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Figure 1: Schematic representation of the stepwise assembly of a triangular-shaped DNA nanotube (N).
Figure 2: Schematic representation of the assembly of the DNA rung (R) and the foundation rung (FR).
Figure 3: Single-molecule characterization of surface-grafted foundation rungs.
Figure 4: Single-molecule imaging of nanotubes prepared after an increasing number of addition cycles, each incorporating a Cy3-tagged rung.
Figure 5: Single-molecule imaging of long DNA nanotubes bearing 20 rungs with alternating Cy3 and Atto647N dyes.


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G.C. and H.F.S. are thankful to the National Science and Engineering Research Council of Canada and the Canada Foundation for Innovation. We are also thankful to Nanoquebec (G.C.), the Canada Institute for Health Research (CIHR) (G.C., H.F.S.) and the Canada Research Chairs program (H.F.S.). H.F.S. is a Cottrell Scholar of the Research Corporation. We are also thankful to the McGill CIHR drug-development training program (A.A.H. and Y.G.), GRASP and FRQNT (A.A.H.) and Vanier Canada (G.D.H.) for Graduate Scholarships.

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All authors contributed ideas, discussed the results and drafted the manuscript. A.A.H., G.C. and H.F.S. designed the study. G.C. and H.F.S. coordinated the study.

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Correspondence to Hanadi F. Sleiman or Gonzalo Cosa.

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The authors declare no competing financial interests.

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Hariri, A., Hamblin, G., Gidi, Y. et al. Stepwise growth of surface-grafted DNA nanotubes visualized at the single-molecule level. Nature Chem 7, 295–300 (2015).

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