Med-X | Optical imaging unveiling metabolic dynamics in cells and organisms during aging and diseases

Cellular metabolism plays a critical role in various physiological and pathological processes. High resolution imaging of intracellular metabolic activities is crucial for understanding many biological pathways, and for facilitating disease prognosis and treatment assessment. Raman scattering (RS) spectroscopy/microscopy, in particular stimulated Raman scattering (SRS), has emerged as a powerful imaging technology for cellular imaging with high specificity, high sensitivity, and subcellular resolution. Since its invention, SRS microscopy imaging has been extensively applied in life science for studying composition, structure, metabolism, development, and disease in biological systems.

The team led by Lingyan Shi and Jorge Villazon from the University of California San Diego reviews the latest applications of SRS imaging, particularly with heavy-water probing, for studying metabolic dynamics of biomolecules in organisms during aging and diseases. Furthermore, future applications and developments of SRS imaging in both life sciences and medicine are discussed.

Since the first application of SRS microscopy for bioimaging, extensive applications of SRS microscopy have been carried out for metabolic imaging in life science. SRS displays many advantages including high sensitivity, high chemical specificity, high spatial resolution (subcellular), imaging speed 1000 times faster than spontaneous Raman, and signal linearly proportion to molecule’s concentration. Employing vibrational tags for SRS imaging enables visualization of small biomolecules metabolism in live cells and organisms. Particularly, D2O is shown as a universal probe to visualize and track metabolic dynamics of various biomolecules simultaneously — improving upon deuterium probes, which can only track a particular biomolecule. The application of deuterium-labeled probes is not solely limited to Drosophila or cellular models, bur has also been applied to a variety of different animal models. Deuterated molecules have been readily utilized in mice; from the study of AMPK regulation in tauopathy mouse brains to measuring protein synthesis through carotid injection of deuterated amino acids to quantifying glucose metabolism via-glucose administration. Furthermore, lipid and protein synthesis in both C. elegans larvae and zebrafish embryos have been imaged following D2O treatment. They envision DO-Raman and DO-SRS imaging can even be implemented in human studies with low heavy water dosage in the near future, enhancing the essential roles this technology will play in studying aging and age-related diseases.

Highlights

• Stimulated Raman scattering microscopy with heavy water probing can be leveraged for imaging vibrational “tags” of molecular bonds.

• The labeling of the carbon-deuterium bonds provides a measurable marker for biomolecule synthesis, particularly for proteins and lipids.

• These metabolic markers can be vital to understanding physiological processes, such as in aging, age-related diseases and cancer.

• The application of this metabolic imaging platform has elicited novel findings on the role of protein and lipid synthesis and turnover.