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Nat Commun. 2018 Aug 6;9(1):2995. doi: 10.1038/s41467-018-05401-3.

Optical imaging of metabolic dynamics in animals.

Author information

1
Department of Chemistry, Columbia University, New York, NY, 10027, USA.
2
Department of Biological Sciences, Columbia University, New York, NY, 10027, USA.
3
Department of Pediatrics, Columbia University, New York, NY, 10027, USA.
4
Department of Chemistry, Columbia University, New York, NY, 10027, USA. wm2256@columbia.edu.
5
Kavli Institute for Brain Science, Columbia University, New York, NY, 10027, USA. wm2256@columbia.edu.

Abstract

Direct visualization of metabolic dynamics in living animals with high spatial and temporal resolution is essential to understanding many biological processes. Here we introduce a platform that combines deuterium oxide (D2O) probing with stimulated Raman scattering (DO-SRS) microscopy to image in situ metabolic activities. Enzymatic incorporation of D2O-derived deuterium into macromolecules generates carbon-deuterium (C-D) bonds, which track biosynthesis in tissues and can be imaged by SRS in situ. Within the broad vibrational spectra of C-D bonds, we discover lipid-, protein-, and DNA-specific Raman shifts and develop spectral unmixing methods to obtain C-D signals with macromolecular selectivity. DO-SRS microscopy enables us to probe de novo lipogenesis in animals, image protein biosynthesis without tissue bias, and simultaneously visualize lipid and protein metabolism and reveal their different dynamics. DO-SRS microscopy, being noninvasive, universally applicable, and cost-effective, can be adapted to a broad range of biological systems to study development, tissue homeostasis, aging, and tumor heterogeneity.

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