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Single-cell biological lasers

Abstract

Since their invention some 50 years ago1, lasers have made a tremendous impact on modern science and technology. Nevertheless, lasing has so far relied on artificial or engineered optical gain materials, such as doped crystals, semiconductors, synthetic dyes and purified gases2,3. Here, we show that fluorescent proteins4,5 in cells are a viable gain medium for optical amplification, and report the first successful realization of biological cell lasers based on green fluorescent protein (GFP). We demonstrate in vitro protein lasers using recombinant GFP solutions and introduce a laser based on single live cells expressing GFP. On optical pumping with nanojoule/nanosecond pulses, individual cells in a high-Q microcavity produce bright, directional and narrowband laser emission, with characteristic longitudinal and transverse modes. Lasing cells remained alive even after prolonged lasing action. Light amplification and lasing from and within biological systems pave the way to new forms of intracellular sensing, cytometry and imaging.

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Figure 1: A protein solution laser.
Figure 2: Laser formed by a single eukaryotic cell.
Figure 3: Comparison of emission from the single-cell laser below and above the lasing threshold.
Figure 4: Combined spatial and spectral analysis of single output pulses of different cell lasers.

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References

  1. Maiman, T. H. Stimulated optical radiation in ruby. Nature 187, 493–494 (1960).

    Article  ADS  Google Scholar 

  2. Weber, M. J. Handbook of Laser Wavelengths (CRC Press, 1999).

    Google Scholar 

  3. Townes, C. H. How the Laser Happened: Adventures of a Scientist (Oxford Univ. Press, 1999).

    Google Scholar 

  4. Shaner, N. C., Steinbach, P. A. & Tsien, R. Y. A guide to choosing fluorescent proteins. Nature Methods 2, 905–909 (2005).

    Article  Google Scholar 

  5. Giepmans, B. N. G., Adams, S. R., Ellisman, M. H. & Tsien, R. Y. Review—the fluorescent toolbox for assessing protein location and function. Science 312, 217–224 (2006).

    Article  ADS  Google Scholar 

  6. Shimomura, O., Johnson, F. H. & Saiga, Y. Extraction, purification and properties of aequorin, a bioluminescent protein from luminous hydromedusan, Aequorea. J. Cell. Comp. Physiol. 59, 223–239 (1962).

    Article  Google Scholar 

  7. Chalfie, M., Tu, Y., Euskirchen, G., Ward, W. W. & Prasher, D. C. Green fluorescent protein as a marker for gene-expression. Science 263, 802–805 (1994).

    Article  ADS  Google Scholar 

  8. Heim, R., Cubitt, A. B. & Tsien, R. Y. Improved green fluorescence. Nature 373, 663–664 (1995).

    Article  ADS  Google Scholar 

  9. Cormack, B. P., Valdivia, R. H. & Falkow, S. Facs-optimized mutants of the green fluorescent protein (gfp). Gene 173, 33–38 (1996).

    Article  Google Scholar 

  10. Shaner, N. C. et al. Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein. Nature Biotechnol. 22, 1567–1572 (2004).

    Article  Google Scholar 

  11. Merzlyak, E. M. et al. Bright monomeric red fluorescent protein with an extended fluorescence lifetime. Nature Methods 4, 555–557 (2007).

    Article  Google Scholar 

  12. Patterson, G. H., Knobel, S. M., Sharif, W. D., Kain, S. R. & Piston, D. W. Use of the green fluorescent protein and its mutants in quantitative fluorescence microscopy. Biophys. J. 73, 2782–2790 (1997).

    Article  Google Scholar 

  13. Pikas, D. J. et al. Nonlinear saturation and lasing characteristics of green fluorescent protein. J. Phys. Chem. B 106, 4831–4837 (2002).

    Article  Google Scholar 

  14. Siegman, A. E. Lasers (University Science Books, 1986).

    Google Scholar 

  15. Chen, Y., Wei, L. N. & Muller, J. D. Probing protein oligomerization in living cells with fluorescence fluctuation spectroscopy. Proc. Natl Acad. Sci. USA 100, 15492–15497 (2003).

    Article  ADS  Google Scholar 

  16. Lu, P., Vogel, C., Wang, R., Yao, X. & Marcotte, E. M. Absolute protein expression profiling estimates the relative contributions of transcriptional and translational regulation. Nature Biotechnol. 25, 117–124 (2007).

    Article  Google Scholar 

  17. Kim, H. & Seed, B. The transcription factor MafB antagonizes antiviral responses by blocking recruitment of coactivators to the transcription factor IRF3. Nature Immunol. 11, 743–750 (2010).

    Article  Google Scholar 

  18. Kemper, B. et al. Integral refractive index determination of living suspension cells by multifocus digital holographic phase contrast microscopy. J. Biomed. Opt. 12, 054009 (2007).

    Article  ADS  Google Scholar 

  19. Svelto, O. Principles of Lasers (Springer-Verlag, 2009).

    Google Scholar 

  20. Bandres, M. A. & Gutiérrez-Vega, J. C. Ince-Gaussian modes of the paraxial wave equation and stable resonators. J. Opt. Soc. Am. A 21, 873–880 (2004).

    Article  ADS  Google Scholar 

  21. Rose, A., Zhu, Z. G., Madigan, C. F., Swager, T. M. & Bulovic, V. Sensitivity gains in chemosensing by lasing action in organic polymers. Nature 434, 876–879 (2005).

    Article  ADS  Google Scholar 

  22. Park, Y. et al. Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum. Proc. Natl Acad. Sci. USA 105, 13730–13735 (2008).

    Article  ADS  Google Scholar 

  23. Klar, T. A., Jakobs, S., Dyba, M., Egner, A. & Hell, S. W. Fluorescence microscopy with diffraction resolution barrier broken by stimulated emission. Proc. Natl Acad. Sci. USA 97, 8206–8210 (2000).

    Article  ADS  Google Scholar 

  24. Westphal, V. et al. Video-rate far-field optical nanoscopy dissects synaptic vesicle movement. Science 320, 246–249 (2008).

    Article  ADS  Google Scholar 

  25. Min, W. et al. Imaging chromophores with undetectable fluorescence by stimulated emission microscopy. Nature 461, 1105–1109 (2009).

    Article  ADS  Google Scholar 

  26. Saar, B. G. et al. Video-rate molecular imaging in vivo with stimulated Raman scattering. Science 330, 1368–1370 (2010).

    Article  ADS  Google Scholar 

  27. Noginov, M. A. et al. Demonstration of a spaser-based nanolaser. Nature 460, 1110–1113 (2009).

    Article  ADS  Google Scholar 

  28. Ma, R.-M., Oulton, R. F., Sorger, V. J., Bartal, G. & Zhang, X. Room-temperature sub-diffraction-limited plasmon laser by total internal reflection. Nature Mater. 10, 110–113 (2011).

    Article  ADS  Google Scholar 

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Acknowledgements

The authors thank Ji-Joon Song (KAIST, Korea) for providing recombinant eGFP solutions, S. Sassi and B. Seed (Harvard Medical School) for the donation of 293ETN cells and support with eGFP transfection, U. Shama for initial testing of a fluorescent protein and W. Farinelli for setting up the OPO system. This work was supported in part by the US National Science Foundation (ECCS-1101947) and the Korea National Research Foundation (R31-2008-000-10071-0). M.C.G. acknowledges financial support from the Bullock-Wellman Fellowship.

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M.C.G. designed and performed the experiments. S.H.Y conceived and supervised the project. Both authors discussed the data and wrote the paper.

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Correspondence to Seok Hyun Yun.

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The authors declare no competing financial interests.

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Gather, M., Yun, S. Single-cell biological lasers. Nature Photon 5, 406–410 (2011). https://doi.org/10.1038/nphoton.2011.99

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