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


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.


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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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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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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).

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