Optical imaging of metabolic dynamics in animals

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • COS Cells
  • Caenorhabditis elegans
  • Carbon / chemistry
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Contrast Media
  • Deuterium
  • Deuterium Oxide
  • HeLa Cells
  • Humans
  • Image Processing, Computer-Assisted
  • Lipid Metabolism
  • Lipids / chemistry
  • Macromolecular Substances
  • Metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • Optical Imaging / methods*
  • Scattering, Radiation
  • Spectrum Analysis, Raman*
  • Zebrafish

Substances

  • Contrast Media
  • Lipids
  • Macromolecular Substances
  • Carbon
  • Deuterium
  • Deuterium Oxide