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A protein transistor made of an antibody molecule and two gold nanoparticles

A Correction to this article was published on 05 April 2012

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Abstract

A major challenge in molecular electronics is to attach electrodes to single molecules in a reproducible manner to make molecular junctions that can be operated as transistors. Several attempts have been made to attach electrodes to proteins, but these devices have been unstable. Here, we show that self-assembly can be used to fabricate, in a highly reproducible manner, molecular junctions in which an antibody molecule (immunoglobulin G) binds to two gold nanoparticles, which in turn are connected to source and drain electrodes. We also demonstrate effective gating of the devices with an applied voltage, and show that the charge transport characteristics of these protein transistors are caused by conformational changes in the antibody. Moreover, by attaching CdSe quantum dots to the antibody, we show that the protein transistor can also be gated by an applied optical field. This approach offers a versatile platform for investigations of single-molecule-based biological functions and might also lead to the large-scale manufacture of integrated bioelectronic circuits.

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Figure 1: Fabrication of the protein transistor.
Figure 2: Electron micrographs of the protein transistor.
Figure 3: Transfer characteristics of the protein transistor.
Figure 4: Effect of the Fc domain on the NDR of pro-T.
Figure 5: Effect of urea denaturation on ISD for the protein transistor.
Figure 6: Light-sensitive gating of the quantum dot-functionalized protein transistor.

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  • 02 March 2012

    In the version of this Article originally published, the address of the first affiliation was incorrect; the correct address should have read 'Biomedical Electronics Translational Research Center, National Chiao Tung University, 1001 University Road, Hsinchu, Taiwan, ROC'. This has now been corrected in the HTML and PDF versions.

References

  1. Trammell, S. A., Spano, A., Price, R. & Lebedev, N. Effect of protein orientation on electron transfer between photosynthetic reaction centers and carbon electrodes. Biosens. Bioelectron. 21, 1023–1028 (2006).

    Article  CAS  Google Scholar 

  2. Ron, I., Friedman, N., Cahen, D. & Sheves, M. Selective electroless deposition of metal clusters on solid-supported bacteriorhodopsin: applications to orientation labeling and electrical contacts. Small 4, 2271–2278 (2008).

    Article  CAS  Google Scholar 

  3. Venkataraman, L., Klare, J. E., Nuckolls, C., Hybertsen, M. S. & Steigerwald, M. L. Dependence of single-molecule junction conductance on molecular conformation. Nature 442, 904–907 (2006).

    Article  CAS  Google Scholar 

  4. Friis, E. P. et al. An approach to long-range electron transfer mechanisms in metalloproteins: in situ scanning tunneling microscopy with submolecular resolution. Proc. Natl Acad. Sci. USA 96, 1379–1384 (1999).

    Article  CAS  Google Scholar 

  5. Stamouli, A., Frenken, J. W. M., Oosterkamp, T. H., Cogdell, R. J. & Aartsma, T. J. The electron conduction of photosynthetic protein complexes embedded in a membrane. FEBS Lett. 560, 109–114 (2004).

    Article  CAS  Google Scholar 

  6. Alessandrini, A., Corni, S. & Facci, P. Unravelling single metalloprotein electron transfer by scanning probe techniques. Phys. Chem. Chem. Phys. 8, 4383–4397 (2006).

    Article  CAS  Google Scholar 

  7. Lee, I., Lee, J. W. & Greenbaum, E. Biomolecular electronics: vectorial arrays of photosynthetic reaction centers. Phys. Rev. Lett. 79, 3294–3297 (1997).

    Article  CAS  Google Scholar 

  8. Axford, D. N. & Davis, J. J. Electron flux through apo- and holoferritin. Nanotechnology 18, 145502 (2007).

    Article  Google Scholar 

  9. Delfino, I. et al. Yeast cytochrome c integrated with electronic elements: a nanoscopic and spectroscopic study down to single-molecule level. J. Phys. Condens. Matter 19, 225009 (2007).

    Article  Google Scholar 

  10. Reiss, B. D., Hanson, D. K. & Firestone, M. A. Evaluation of the photosynthetic reaction center protein for potential use as a bioelectronic circuit element. Biotechnol. Progr. 23, 985–989 (2007).

    Article  CAS  Google Scholar 

  11. Xu, D. G., Watt, G. D., Harb, J. N. & Davis, R. C. Electrical conductivity of ferritin proteins by conductive AFM. Nano Lett. 5, 571–577 (2005).

    Article  CAS  Google Scholar 

  12. Zhao, J. W., Davis, J. J., Sansom, M. S. P. & Hung, A. Exploring the electronic and mechanical properties of protein using conducting atomic force microscopy. J. Am. Chem. Soc. 126, 5601–5609 (2004).

    Article  CAS  Google Scholar 

  13. Reed, M. A., Zhou, C., Muller, C. J., Burgin, T. P. & Tour, J. M. Conductance of a molecular junction. Science 278, 252–254 (1997).

    Article  CAS  Google Scholar 

  14. Haick, H. & Cahen, D. Making contact: connecting molecules electrically to the macroscopic world. Prog. Surf. Sci. 83, 217–261 (2008).

    Article  CAS  Google Scholar 

  15. Haick, H. & Cahen, D. Contacting organic molecules by soft methods: towards molecule-based electronic devices. Acc. Chem. Res. 41, 359–366 (2008).

    Article  CAS  Google Scholar 

  16. Quek, S. Y. et al. Amine-gold linked single-molecule circuits: experiment and theory. Nano Lett. 7, 3477–3482 (2007).

    Article  CAS  Google Scholar 

  17. Cheng, Z. L. et al. In situ formation of highly conducting covalent Au–C contacts for single-molecule junctions. Nature Nanotech. 6, 353–357 (2011).

    Article  CAS  Google Scholar 

  18. Gray, H. B. & Winkler, J. R. Electron transfer in proteins. Annu. Rev. Biochem. 65, 537–561 (1996).

    Article  CAS  Google Scholar 

  19. Gray, H. B. & Winkler, J. R. Electron tunneling through proteins. Q. Rev. Biophys. 36, 341–372 (2003).

    Article  CAS  Google Scholar 

  20. Heath, J. R. & Ratner, M. A. Molecular electronics. Phys. Today 56, 43–49 (May 2003).

    Article  CAS  Google Scholar 

  21. Joachim, C. & Ratner, M. A. Molecular electronics: some views on transport junctions and beyond. Proc. Natl Acad. Sci. USA 102, 8801–8808 (2005).

    Article  CAS  Google Scholar 

  22. Ron, I. et al. Proteins as electronic materials: electron transport through solid-state protein monolayer junctions. J. Am. Chem. Soc. 132, 4131–4140 (2010).

    Article  CAS  Google Scholar 

  23. Carmeli, I., Frolov, L., Carmeli, C. & Richter, S. Photovoltaic activity of photosystem I-based self-assembled monolayer. J. Am. Chem. Soc. 129, 12352–12353 (2007).

    Article  CAS  Google Scholar 

  24. Das, R. et al. Integration of photosynthetic protein molecular complexes in solid-state electronic devices. Nano Lett. 4, 1079–1083 (2004).

    Article  CAS  Google Scholar 

  25. Maruccio, G. et al. Towards protein field-effect transistors: report and model of prototype. Adv. Mater. 17, 816–822 (2005).

    Article  CAS  Google Scholar 

  26. Maruccio, G. et al. Protein conduction and negative differential resistance in large-scale nanojunction arrays. Small 3, 1184–1188 (2007).

    Article  CAS  Google Scholar 

  27. Mentovich, E. D., Belgorodsky, B., Kalifa, I., Cohen, H. & Richter, S. Large-scale fabrication of 4-nm-channel vertical protein-based ambipolar transistors. Nano Lett. 9, 1296–1300 (2009).

    Article  CAS  Google Scholar 

  28. Chen, Y. S., Hung, Y. C., Chen, K. C. & Huang, G. S. Detection of gold nanoparticles using an immunoglobulin-coated piezoelectric sensor. Nanotechnology 19, 495502 (2008).

    Article  Google Scholar 

  29. Huang, G. S., Chen, Y. S. & Yeh, H. W. Measuring the flexibility of immunoglobulin by gold nanoparticles. Nano Lett. 6, 2467–2471 (2006).

    Article  CAS  Google Scholar 

  30. Chen, J., Reed, M. A., Rawlett, A. M. & Tour, J. M. Large on–off ratios and negative differential resistance in a molecular electronic device. Science 286, 1550–1552 (1999).

    Article  CAS  Google Scholar 

  31. Chen, J. et al. Room-temperature negative differential resistance in nanoscale molecular junctions. Appl. Phys. Lett. 77, 1224–1226 (2000).

    Article  CAS  Google Scholar 

  32. Farver, O. & Pecht, I. Long-range intramolecular electron-transfer in azurins. J. Am. Chem. Soc. 114, 5764–5767 (1992).

    Article  CAS  Google Scholar 

  33. Zimbovskaya, N. A. & Pederson, M. R. Negative differential resistance in molecular junctions: effect of the electronic structure of the electrodes. Phys. Rev. B 78, 153105 (2008).

    Article  Google Scholar 

  34. Guisinger, N. P., Greene, M. E., Basu, R., Baluch, A. S. & Hersam, M. C. Room temperature negative differential resistance through individual organic molecules on silicon surfaces. Nano Lett. 4, 55–59 (2004).

    Article  CAS  Google Scholar 

  35. Mentovich, E. D., Belgorodsky, B. & Richter, S. Resolving the mystery of the elusive peak: negative differential resistance in redox proteins. J. Phys. Chem. Lett. 2, 1125–1128 (2011).

    Article  CAS  Google Scholar 

  36. Maruccio, G. et al. Field effect transistor based on a modified DNA base. Nano Lett. 3, 479–483 (2003).

    Article  CAS  Google Scholar 

  37. Appenzeller, J. et al. Field-modulated carrier transport in carbon nanotube transistors. Phys. Rev. Lett. 89, 126801 (2002).

    Article  CAS  Google Scholar 

  38. Tans, S. J., Verschueren, A. R. M. & Dekker, C. Room-temperature transistor based on a single carbon nanotube. Nature 393, 49–52 (1998).

    Article  CAS  Google Scholar 

  39. DiBenedetto, S. A., Facchetti, A., Ratner, M. A. & Marks, T. J. Molecular self-assembled monolayers and multilayers for organic and unconventional inorganic thin-film transistor applications. Adv. Mater. 21, 1407–1433 (2009).

    Article  CAS  Google Scholar 

  40. Ramachandran, G. K. et al. A bond-fluctuation mechanism for stochastic switching in wired molecules. Science 300, 1413–1416 (2003).

    Article  CAS  Google Scholar 

  41. Yao, J., Zhong, L., Natelson, D. & Tours, J. M. Silicon oxide: a non-innocent surface for molecular electronics and nanoelectronics studies. J. Am. Chem. Soc. 133, 941–948 (2011).

    Article  CAS  Google Scholar 

  42. Kamat, P. V. Quantum dot solar cells. Semiconductor nanocrystals as light harvesters. J. Phys. Chem. C 112, 18737–18753 (2008).

    Article  CAS  Google Scholar 

  43. Wolynes, P. G. Biomolecular folding in vacuo!!!(?). Proc. Natl Acad. Sci. USA 92, 2426–2427 (1995).

    Article  CAS  Google Scholar 

  44. Breuker, K., Bruschweiler, S. & Tollinger, M. Electrostatic stabilization of a native protein structure in the gas phase. Angew. Chem. Int. Ed. 50, 873–877 (2011).

    Article  CAS  Google Scholar 

  45. Iavarone, A. T., Patriksson, A., van der Spoel, D. & Parks, J. H. Fluorescence probe of Trp-cage protein conformation in solution and in gas phase. J. Am. Chem. Soc. 129, 6726–6735 (2007).

    Article  CAS  Google Scholar 

  46. Patriksson, A., Marklund, E. & van der Spoel, D. Protein structures under electrospray conditions. Biochemistry 46, 933–945 (2007).

    Article  CAS  Google Scholar 

  47. Burton, R. E., Huang, G. S., Daugherty, M. A., Fullbright, P. W. & Oas, T. G. Microsecond protein folding through a compact transition state. J. Mol. Biol. 263, 311–322 (1996).

    Article  CAS  Google Scholar 

  48. Page, C. C., Moser, C. C. & Dutton, P. L. Mechanism for electron transfer within and between proteins. Curr. Opin. Chem. Biol. 7, 551–556 (2003).

    Article  CAS  Google Scholar 

  49. Brown, K. R., Walter, D. G. & Natan, M. J. Seeding of colloidal Au nanoparticle solutions. 2. Improved control of particle size and shape. Chem. Mater. 12, 306–313 (2000).

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by the ‘Aim for the Top University Plan’ of National Chiao Tung University and the Ministry of Education, Taiwan, ROC. The authors also acknowledge funding support from the Air Force Office of Scientific Research (AFOSR, FA2386-11-1-4094).

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Y.S.C. and G.S.H. are responsible for the study concept and design. G.S.H. and M.Y.H. prepared the manuscript. Y.S.C. and M.Y.H. carried out the experiments and performed the data analysis.

Corresponding author

Correspondence to G. Steven Huang.

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The authors declare no competing financial interests.

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Chen, YS., Hong, MY. & Huang, G. A protein transistor made of an antibody molecule and two gold nanoparticles. Nature Nanotech 7, 197–203 (2012). https://doi.org/10.1038/nnano.2012.7

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