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A proximity-based programmable DNA nanoscale assembly line

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Abstract

Our ability to synthesize nanometre-scale chemical species, such as nanoparticles with desired shapes and compositions, offers the exciting prospect of generating new functional materials and devices by combining them in a controlled fashion into larger structures. Self-assembly can achieve this task efficiently, but may be subject to thermodynamic and kinetic limitations: reactants, intermediates and products may collide with each other throughout the assembly time course to produce non-target species instead of target species. An alternative approach to nanoscale assembly uses information-containing molecules such as DNA1 to control interactions and thereby minimize unwanted cross-talk between different components. In principle, this method should allow the stepwise and programmed construction of target products by linking individually selected nanoscale components—much as an automobile is built on an assembly line. Here we demonstrate that a nanoscale assembly line can be realized by the judicious combination of three known DNA-based modules: a DNA origami2 tile that provides a framework and track for the assembly process, cassettes containing three independently controlled two-state DNA machines that serve as programmable cargo-donating devices3,4 and are attached4,5 in series to the tile, and a DNA walker that can move on the track from device to device and collect cargo. As the walker traverses the pathway prescribed by the origami tile track, it sequentially encounters the three DNA devices, each of which can be independently switched between an ‘ON’ state, allowing its cargo to be transferred to the walker, and an ‘OFF’ state, in which no transfer occurs. We use three different types of gold nanoparticle species as cargo and show that the experimental system does indeed allow the controlled fabrication of the eight different products that can be obtained with three two-state devices.

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Figure 1: The molecular assembly line and its operation.
Figure 2: Details of the walker, movement and cargo transfer.
Figure 3: The eight products of the assembly line.

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Acknowledgements

We are grateful to J. Canary, H. Yan, C. Mao and R. Sha for comments on this manuscript. This research has been supported by the following grants: GM-29544 from the US National Institute of General Medical Sciences, CTS-0608889 and CCF-0726378 from the US National Science Foundation, 48681-EL and W911NF-07-1-0439 from the US Army Research Office, N000140910181 and N000140911118 from the US Office of Naval Research and a grant from the W. M. Keck Foundation (to N.C.S.); and 2007CB925101 from the National Basic Research Program of China and 20721002 from the National Natural Science Foundation of China (to S.-J.X.). H.G. thanks New York University for a Dissertation Fellowship and J.C. thanks the Chinese Scholarship Council for a research fellowship.

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Authors

Contributions

H.G. and J.C. did the research, analysed data and wrote the paper. S.-J.X. analysed data and wrote the paper. N.C.S. designed the project, analysed data and wrote the paper.

Corresponding author

Correspondence to Nadrian C. Seeman.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file comprises Supplementary Figures S1- S12 with legends and Supplementary Table S1 as follows: origami design (figure S1) and sequence; cassette design and sequence (figures S2-S4); walker locomotion and sequence design (figure S5); nondenaturing gels of the cassettes and walker (S6); agarose gels of the DNA-nanoparticle conjugates (figure S7), AFM images of the movement of the walker on the origami (figure S8); AFM images of the dynamic switching of each cassette on the origami (figure S9); zoomed TEM images for statistical analysis (figures S10 and S11); the distance distribution between particles on the walker (figure S12), and the statistical analysis for the different additions (table S1). (PDF 4267 kb)

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Gu, H., Chao, J., Xiao, SJ. et al. A proximity-based programmable DNA nanoscale assembly line. Nature 465, 202–205 (2010). https://doi.org/10.1038/nature09026

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