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Live-cell imaging of alkyne-tagged small biomolecules by stimulated Raman scattering

Nature Methods volume 11, pages 410–412 (2014)Cite this article

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Abstract

Sensitive and specific visualization of small biomolecules in living systems is highly challenging. We report stimulated Raman-scattering imaging of alkyne tags as a general strategy for studying a broad spectrum of small biomolecules in live cells and animals. We demonstrate this technique by tracking alkyne-bearing drugs in mouse tissues and visualizing de novo synthesis of DNA, RNA, proteins, phospholipids and triglycerides through metabolic incorporation of alkyne-tagged small precursors.

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Figure 1: Bond-selective SRS imaging of alkynes as nonlinear vibrational tags.
Figure 2: Live SRS imaging of de novo synthesis of DNA, RNA, proteomes, phospholipids and triglycerides by metabolic incorporation of alkyne-tagged small precursors.

References

  1. Zhang, J., Campbell, R.E., Ting, A.Y. & Tsien, R.Y. Nat. Rev. Mol. Cell Biol. 3, 906–918 (2002).

    Article  CAS  Google Scholar 

  2. Sasic, S. & Ozaki, Y. Raman, Infrared, and Near-infrared Chemical Imaging (Wiley, 2011).

  3. Cheng, J.-X. & Xie, X.S. Coherent Raman Scattering Microscopy (CRC Press, 2012).

  4. Masters, B.R. & So, P.T.C. Handbook of Biomedical Nonlinear Optical Microscopy (Oxford University Press, 2008).

  5. Prescher, J.A. & Bertozzi, C.R. Nat. Chem. Biol. 1, 13–21 (2005).

    Article  CAS  Google Scholar 

  6. Grammel, M. & Hang, H.C. Nat. Chem. Biol. 9, 475–484 (2013).

    Article  CAS  Google Scholar 

  7. Salic, A. & Mitchison, T.J. Proc. Natl. Acad. Sci. USA 105, 2415–2420 (2008).

    Article  CAS  Google Scholar 

  8. Jao, C.Y. & Salic, A. Proc. Natl. Acad. Sci. USA 105, 15779–15784 (2008).

    Article  CAS  Google Scholar 

  9. Beatty, K.E. et al. Angew. Chem. Int. Ed. 45, 7364–7367 (2006).

    Article  CAS  Google Scholar 

  10. Jao, C.Y., Roth, M., Welti, R. & Salic, A. Proc. Natl. Acad. Sci. USA 106, 15332–15337 (2009).

    Article  CAS  Google Scholar 

  11. Hang, H.C., Wilson, J.P. & Charron, G. Acc. Chem. Res. 44, 699–708 (2011).

    Article  CAS  Google Scholar 

  12. Baskin, J.M. et al. Proc. Natl. Acad. Sci. USA 104, 16793–16797 (2007).

    Article  CAS  Google Scholar 

  13. Lin-Vien, D., Colthup, N.B., Fateley, W.G. & Grasselli, J.G. The Handbook of Infrared and Raman Characteristic Frequencies of Organic Molecules 95–104 (Academic Press, 1991).

  14. Wei, L., Shen, Y., Yong, Y., Wang, M. & Min, W. Proc. Natl. Acad. Sci. USA 110, 11226–11231 (2013).

    Article  CAS  Google Scholar 

  15. Yamakoshi, H. et al. J. Am. Chem. Soc. 133, 6102–6105 (2011).

    Article  CAS  Google Scholar 

  16. Yamakoshi, H. et al. J. Am. Chem. Soc. 134, 20681–20689 (2012).

    Article  CAS  Google Scholar 

  17. Min, W., Freudiger, C.W., Lu, S. & Xie, X.S. Annu. Rev. Phys. Chem. 62, 507–530 (2011).

    Article  CAS  Google Scholar 

  18. Freudiger, C.W. et al. Science 322, 1857–1861 (2008).

    Article  CAS  Google Scholar 

  19. Moore, K.J. & Tabas, I. Cell 145, 341–355 (2011).

    Article  CAS  Google Scholar 

  20. Ashrafi, K. et al. Nature 421, 268–272 (2003).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank L. Zhang, L. Brus, V.W. Cornish, D. Peterka and R. Yuste for helpful discussions. We are grateful to Y. Shin and X. Gao for technical assistance. W.M. acknowledges support from Columbia University, a US National Institutes of Health Director's New Innovator Award, the US Army Research Office (W911NF-12-1-0594) and an Alfred P. Sloan Research Fellowship.

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Authors and Affiliations

  1. Department of Chemistry, Columbia University, New York, New York, USA

    Lu Wei, Fanghao Hu, Yihui Shen, Zhixing Chen & Wei Min

  2. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA

    Yong Yu, Chih-Chun Lin & Meng C Wang

  3. Kavli Institute for Brain Science, Columbia University, New York, New York, USA

    Wei Min

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  1. Lu Wei
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Contributions

L.W., F.H., Y.S., Z.C., Y.Y., C.-C.L. and M.C.W. performed experiments and analyzed data. L.W. and W.M. conceived the concept, designed the experiments and wrote the paper.

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Correspondence to Wei Min.

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Competing interests

Columbia University, which L.W., F.H., Y.S., Z.C. and W.M. are affiliated with, has filed a patent application based on this work.

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Wei, L., Hu, F., Shen, Y. et al. Live-cell imaging of alkyne-tagged small biomolecules by stimulated Raman scattering. Nat Methods 11, 410–412 (2014). https://doi.org/10.1038/nmeth.2878

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