Seminar: "Live cell metabolic imaging with sub-micron IR microscopy"

To survive, cells must sense and rapidly adapt their metabolism to environmental stress. Fatty acid metabolism, including endogenous de novo biosynthesis and exogenous uptake, plays a central role in meeting fluctuating cellular energy needs. Understanding the dynamics of competing fatty acid pathways across the cell, their variations across cell types, and their responses to cellular stresses is crucial, as dysregulation of fatty acid metabolism is implicated in diseases including cancer and metabolic syndrome. However, measuring fatty acid metabolism inside the cell is difficult because labeling lipids and their precursors is not trivial. Existing techniques only measure parts of fatty acid metabolism, like glucose uptake, or do not provide subcellular spatial resolution. Recently, we showed that optical photothermal infrared microscopy (O-PTIR) is a powerful tool for tracking de novo lipogenesis with spatial resolution exceeding 500 nm. Here, we employ orthogonal isotopic labeling of glucose and oleic acid to concomitantly monitor endogenous synthesis and exogenous uptake of fatty acids in live and fixed hepatocytes and adipocytes. Leveraging O-PTIR’s high spatial resolution, we observe differences in rates of de novo lipogenesis and fatty acid scavenging at distinct locations across the cell. Furthermore, we assign lipid composition, including lipid saturation levels using hyperspectral imaging. This comprehensive approach provides a foundation for understanding lipid dysregulation and engineering effective metabolic treatment strategies.

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Meeting ID: 912 1233 8898
Passcode: 805224

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