Protein synthesis observed in vivo using injected deuterated amino acids and Raman scattering

The ability to visualize protein synthesis in vivo could enable biologists and medical researchers to better understand how proteins affect biological systems and quickly determine whether a tissue is normal or diseased. Current methods for observing protein synthesis in living organisms include autoradiography, mass spectroscopy and fluorescence microscopy. But these have fallen short of capturing protein metabolism because they cannot achieve the necessary subcellular resolution, or because the molecular labels are too bulky.

Shi et al. now report in APL Photonics that they have optimized their method for visualizing newly synthesized proteins in cultured mammalian cells and tissues for use in vivo. The optimized imagining method uses stimulated Raman scattering microscopy to observe deuterated amino acids (dAA) that have been absorbed into live cells. And by employing intracarotid arterial injection of dAA into mouse models, instead of administering the dAA orally, the authors enhanced labeling efficiency. They could better view protein metabolic activities at different time points and in a greater number of organs and tissues.

Results from demonstrations using mouse models showed that the optimized imaging method could be used to visualize protein synthesis in the cerebral cortex, cerebellar cortex and hippocampal regions of the brain. It could also apply to visualizing secretory structures at different time points in the choroid plexus, the pancreas and the liver.

The authors also observed protein synthesis in a xenograft colon cancer tumor and clearly distinguished the cancerous tissue from the surrounding normal tissues. Based on these results, the researchers say their imaging method has the potential to be an effective tool for the study of complex protein metabolism in both healthy and diseased tissues in living organisms.

Source: “Visualizing protein synthesis in mice with in vivo labeling of deuterated amino acids using vibrational imaging,” by Lingyan Shi, Yihui Shen, and Wei Min, APL Photonics (2018). The article can be accessed at https://doi.org/10.1063/1.5028134 .