DNA-programmable nanoparticle crystallization


It was first shown1,2 more than ten years ago that DNA oligonucleotides can be attached to gold nanoparticles rationally to direct the formation of larger assemblies. Since then, oligonucleotide-functionalized nanoparticles have been developed into powerful diagnostic tools3,4 for nucleic acids and proteins, and into intracellular probes5 and gene regulators6. In contrast, the conceptually simple yet powerful idea that functionalized nanoparticles might serve as basic building blocks that can be rationally assembled through programmable base-pairing interactions into highly ordered macroscopic materials remains poorly developed. So far, the approach has mainly resulted in polymerization, with modest control over the placement of, the periodicity in, and the distance between particles within the assembled material. That is, most of the materials obtained thus far are best classified as amorphous polymers7,8,9,10,11,12,13,14,15,16, although a few examples of colloidal crystal formation exist8,16. Here, we demonstrate that DNA can be used to control the crystallization of nanoparticle–oligonucleotide conjugates to the extent that different DNA sequences guide the assembly of the same type of inorganic nanoparticle into different crystalline states. We show that the choice of DNA sequences attached to the nanoparticle building blocks, the DNA linking molecules and the absence or presence of a non-bonding single-base flexor can be adjusted so that gold nanoparticles assemble into micrometre-sized face-centred-cubic or body-centred-cubic crystal structures. Our findings thus clearly demonstrate that synthetically programmable colloidal crystallization is possible, and that a single-component system can be directed to form different structures.

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Figure 1: Scheme of gold nanoparticle assembly method.
Figure 2: f.c.c. gold nanoparticle SAXS pattern.
Figure 3: b.c.c. gold nanoparticle SAXS pattern.
Figure 4: Changing DNA length and gold nanoparticle size in the binary-component assembly scheme (b.c.c.).


  1. 1

    Mirkin, C. A., Letsinger, R. L., Mucic, R. C. & Storhoff, J. J. A DNA-based method for rationally assembling nanoparticles into macroscopic materials. Nature 382, 607–609 (1996)

    ADS  CAS  Article  Google Scholar 

  2. 2

    Alivisatos, A. P. et al. Organization of ‘nanocrystal molecules’ using DNA. Nature 382, 609–611 (1996)

    ADS  CAS  Article  Google Scholar 

  3. 3

    Rosi, N. L. & Mirkin, C. A. Nanostructures in biodiagnostics. Chem. Rev. 105, 1547–1562 (2005)

    CAS  Article  Google Scholar 

  4. 4

    Ozin, G. A. & Arsenault, A. C. Nanochemistry: A Chemical Approach to Nanomaterials (Royal Society of Chemistry, Cambridge, UK, 2005)

    Google Scholar 

  5. 5

    Seferos, D. S., Giljohann, D. A., Hill, H. D., Prigodich, A. E. & Mirkin, C. A. Nano-flares: Probes for transfection and mRNA detection in living cells. J. Am. Chem. Soc. 129, 15477–15479 (2007)

    CAS  Article  Google Scholar 

  6. 6

    Rosi, N. L. et al. Oligonucleotide-modified gold nanoparticles for intracellular gene regulation. Science 312, 1027–1030 (2006)

    ADS  CAS  Article  Google Scholar 

  7. 7

    Park, S. J., Lazarides, A. A., Storhoff, J. J., Pesce, L. & Mirkin, C. A. The structural characterization of oligonucleotide-modified gold nanoparticle networks formed by DNA hybridization. J. Phys. Chem. B 108, 12375–12380 (2004)

    CAS  Article  Google Scholar 

  8. 8

    Biancaniello, P. L., Kim, A. J. & Crocker, J. C. Colloidal interactions and self-assembly using DNA hybridization. Phys. Rev. Lett. 94, 058302 (2005)

    ADS  Article  Google Scholar 

  9. 9

    Park, S. J., Lazarides, A. A., Mirkin, C. A. & Letsinger, R. L. Directed assembly of periodic materials from protein and oligonucleotide-modified nanoparticle building blocks. Angew. Chem. Int. Edn 40, 2909–2912 (2001)

    CAS  Article  Google Scholar 

  10. 10

    Park, S. Y. & Stroud, D. Theory of melting and the optical properties of gold/DNA nanocomposites. Phys. Rev. B 67, 212202 (2003)

    ADS  Article  Google Scholar 

  11. 11

    Park, S. Y. & Stroud, D. Structure formation, melting, and optical properties of gold/DNA nanocomposites: Effects of relaxation time. Phys. Rev. B 68, 224201 (2003)

    ADS  Article  Google Scholar 

  12. 12

    Park, S. Y., Lee, J. S., Georganopoulou, D., Mirkin, C. A. & Schatz, G. C. Structures of DNA-linked nanoparticle aggregates. J. Phys. Chem. B 110, 12673–12681 (2006)

    CAS  Article  Google Scholar 

  13. 13

    Velev, O. D. Self-assembly of unusual nanoparticle crystals. Science 312, 376–377 (2006)

    CAS  Article  Google Scholar 

  14. 14

    Strable, E., Johnson, J. E. & Finn, M. G. Natural nanochemical building blocks: icosahedral virus particles organized by attached oligonucleotides. Nano Lett. 4, 1385–1389 (2004)

    ADS  CAS  Article  Google Scholar 

  15. 15

    Nykypanchuk, D., Maye, M. M., der Lelie, D. & Gang, O. DNA-based approach for interparticle interaction control. Langmuir 23, 6305–6314 (2007)

    CAS  Article  Google Scholar 

  16. 16

    Kim, A. J., Biancaniello, P. L. & Crocker, J. C. Engineering DNA-mediated colloidal crystallization. Langmuir 22, 1991–2001 (2001)

    Article  Google Scholar 

  17. 17

    Hurst, S. J., Lytton-Jean, A. K. R. & Mirkin, C. A. Maximizing DNA loading on a range of gold nanoparticle sizes. Anal. Chem. 78, 8313–8318 (2006)

    CAS  Article  Google Scholar 

  18. 18

    Huo, F., Lytton-Jean, A. K. R. & Mirkin, C. A. Asymmetric functionalization of nanoparticles based on thermally addressable DNA interconnects. Adv. Mat. 18, 2304–2306 (2006)

    CAS  Article  Google Scholar 

  19. 19

    Redl, F. X., Cho, K. S., Murray, C. B. & O'Brien, S. Three-dimensional binary superlattices of magnetic nanocrystals and semiconductor quantum dots. Nature 423, 968–971 (2003)

    ADS  CAS  Article  Google Scholar 

  20. 20

    Leunissen, M. E. et al. Ionic colloidal crystals of oppositely charged particles. Nature 437, 235–240 (2005)

    ADS  CAS  Article  Google Scholar 

  21. 21

    Bartlett, P. & Campbell, A. I. Three-dimensional binary superlattices of oppositely charged colloids. Phys. Rev. Lett. 95, 128302 (2005)

    ADS  Article  Google Scholar 

  22. 22

    Shevchenko, E. V., Talapin, D. V., Kotov, N. A., O’Brien, S. & Murray, C. B. Structural diversity in binary nanoparticle superlattices. Nature 439, 55–59 (2006)

    ADS  CAS  Article  Google Scholar 

  23. 23

    Kalsin, A. M. et al. Electrostatic self-assembly of binary nanoparticle crystals with a diamond-like lattice. Science 312, 420–424 (2006)

    ADS  CAS  Article  Google Scholar 

  24. 24

    Donev, A., Torquato, S., Stillinger, F. H. & Connelly, R. A linear programming algorithm to test for jamming in hard-sphere packings. J. Comput. Phys. 197, 139–166 (2004)

    ADS  MathSciNet  Article  Google Scholar 

  25. 25

    Cullity, B. D. Elements of X-Ray Diffraction (Addison-Wesley, Reading, Massachusetts, 1978)

    Google Scholar 

  26. 26

    Frenkel, D. Colloidal crystals: plenty of room at the top. Nature Mater. 5, 85–86 (2006)

    ADS  CAS  Article  Google Scholar 

  27. 27

    Kiely, C. J., Fink, J., Brust, M., Bethell, D. & Schiffrin, D. J. Spontaneous ordering of bimodal ensembles of nanoscopic gold clusters. Nature 396, 444–446 (1998)

    ADS  CAS  Article  Google Scholar 

  28. 28

    Hoogerbrugge, P. J. & Koelman, J. M. V. A. Simulating microscopic hydrodynamic phenomena with dissipative particle dynamics. Europhys. Lett. 19, 155–160 (1992)

    ADS  Article  Google Scholar 

  29. 29

    Español, P. & Warren, P. Statistical mechanics of dissipative particle dynamics. Europhys. Lett. 30, 191–196 (1995)

    ADS  Article  Google Scholar 

  30. 30

    Xu, X.-Y., Rosi, N. L., Wang, Y., Huo, F. & Mirkin, C. A. Asymmetric functionalization of gold nanoparticles with oligonucleotides. J. Am. Chem. Soc. 128, 9286–9287 (2006)

    CAS  Article  Google Scholar 

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C.A.M. acknowledges the AFOSR and NSF for support of this work. C.A.M is also grateful for a NIH Director’s Pioneer Award. S.Y.P. and G.C.S. were supported by the NSF. S.Y.P. and G.C.S. thank S. Torquato for providing numerical model output and S. Ryu for discussions. We thank S. Seifert for help with the SAXS set-up. We thank the Argonne National Laboratory for the use of the APS, supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences.

Author Contributions C.A.M. was the originator of the concept of programmable colloidal crystallization with DNA. A.K.R.L.-J. and C.A.M were responsible for the synthetic components of the project and sequence design. S.Y.P. and G.C.S. were responsible for the theoretical components of the project. S.W. designed the SAXS set-up. S.Y.P., A.K.R.L.-J. and B.L. designed and performed SAXS experiments. S.Y.P. and B.L. analysed the SAXS data. All authors contributed to the writing of the manuscript.

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Correspondence to Chad A. Mirkin.

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The file contains Supplementary Notes and Supplementary Figures S1-S5 with Legends. This file was replaced on 4 February 2008. (PDF 363 kb)

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Park, S., Lytton-Jean, A., Lee, B. et al. DNA-programmable nanoparticle crystallization. Nature 451, 553–556 (2008). https://doi.org/10.1038/nature06508

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