ITP South Building 6420

Understanding the dynamics and heterogeneity of metabolism in a single cell or a multicellular organism is essential to unraveling the mechanistic basis of many biological processes. It is the synthesis, transformation and degradation (the definition of metabolism) of biomolecules that carry out the genetic blueprint. Traditional imaging methods such as MRI, PET, fluorescence, and mass spectrometry have fundamental limitations, for example, conventional methods can only detect the early stages of glucose metabolism (catabolism), but cannot monitor or visualize the process from glucose anabolism to different macromolecule synthesis in situ. Being an emerging non-linear vibrational imaging microscopy technique, stimulated Raman scattering (SRS) can generate chemical specific imaging in situ with high resolution, deep penetration, and quantitative capability. In the present work, we developed new methods that combine deuterium (D)-labeled metabolites (such as heavy water, D-glucose, D-fatty acids, and D-amino acids) probing and SRS microscopy to visualize metabolic dynamics in live cells and animals. The incorporation of D-labeled metabolites into new biomolecules would carry the carbon-deuterium (C-D) bonds into macromolecules including proteins, lipids, DNA/RNA, and carbohydrates. Within the broad vibrational spectra of C-D bonds, we discovered macromolecule-specific Raman shifts and developed spectral unmixing methods to obtain C-D signals with macromolecular selectivity. Applying this method, we were able to study the myelination in the postnatal mouse brain, identify tumor boundaries, examine the intra-tumoral metabolic heterogeneity, and differentiate protein/lipid metabolism during aging process. This technology platform is non-invasive, universal applicable, and can be adapted into a broad range of biological studies such as development, aging, homeostasis, tumor progression, and more.