Mid-Infrared Photothermal Imaging Unveils Altered Stearoyl-CoA desaturase (SCD) Activity in Ovarian Cancer Cells

Abstract

Stearoyl-CoA desaturase (SCD)-catalyzed fatty acid desaturation plays a key role in cancer metabolism reprogramming. While existing approaches enable quantification of SCD expression, directly monitoring in situ SCD enzymatic activity alterations remains challenging. Here, we report a strategy to measure intracellular SCD activity alterations and SCD product distributions by mid-infrared photothermal (MIP) imaging. Fully deuterated palmitic acid (PA-d31) is repurposed here as a chemical probe to report the SCD activity via a new peak at 2246 cm-1, corresponding to the stretching of D-C=C-D bonds in the SCD product. The MIP intensity ratio between the product-associated signal and the total C-D signal defines the apparent SCD activity index. By visualization of SCD-catalyzed metabolic conversion, our approach reveals altered SCD activity in cisplatin-treated ovarian cancer cells, ovarian cancer stem cells and cells fed with oleic acid. Non-uniform distributions of the SCD product are also observed. These results establish bio-orthogonal MIP microscopy as a platform for studying intracellular enzymatic reactions in living systems.