Glucose is the primary source of energy for most of the living organisms. The uptake of this hydrophilic molecule is mediated by transporters of the cell membrane that facilitate its entry into the hydrophobic plasma membrane, and this pathway is biologically activated. If there is a disturbance in this well regulated pathway, the cellular metabolic demands are affected. Monitoring the glucose intake has been a huge challenge, and the efforts have not been fruitful with techniques such as positron emission tomography (PET), magnetic resonance imaging (MRI) and fluorescence microscopy.
Researchers from the Columbia University, New York have generated a new platform to image the glucose uptake in live cells and tissues by Stimulated Raman Scattering (SRS). SRS works by detecting the vibrations in chemical bonds between atoms and SRS microscopy aids in real-time, three-dimensional bioimaging free of fluorescent labels that can hinder many biological processes.
Cellular imagining of glucose uptake having glucose analogues conjugated with fluorescent probes has limitations of altering glucose’s hydrophilic property, non specific interactions which would bias the true distribution of glucose.
Hu and the team developed a novel glucose analogue named 3-O-propargyl-d-glucose (3-OPG) that surpasses these limitations and makes the imagining of vibrationally labelled D-glucose by SRS very easy. Compared with fluorophores, the alkyne tag (CC) in 3-OPG is physically much smaller and chemically inert in cells. 3-OPG not only preserves the hydrophilic nature, weight of glucose but also prevent its non-specific interactions in cells and tissues. Detection-wise, the alkyne tag exhibits a pronounced CC stretching Raman peak and these alkyne tags have been coupled to SRS microscopy as a powerful vibrational label for metabolic imaging in live cells with high sensitivity, specificity, and biocompatibility. 3-OPG also has high translocation efficiency (for example, crossing the blood–brain barrier).
Therefore, by targeting the unique vibrational signature of alkyne tags and the use of near-infrared lasers SRS imaging of 3-OPG uptake could be a valuable method to study energy demands and metabolic status in living systems with subcellular resolution and minimal perturbation. The researchers hope that this technique can help to study the glucose uptake especially in brain and malignant tumors. These tumors are inherently in high demand of energy and this method could be helpful in understanding the detailed pathpysiology of tumors and generate insights into the development of targeted therapeutics.