Signaling lipids play a key role in cell fate regulation, and their deregulation is responsible for cancer, inflammation, and metabolic diseases, making them an attractive target for therapeutic intervention. Probing signaling lipids are difficult because of their low abundance, high lipophilicity, and inherent instability. Traditionally, genetically encoded photoactivatable fluorescent proteins (FP) are used to track lipids because of the simplicity of creating a gene construct. However, FPs cause undesired aggregation and altered protein functions due to their larger relative size compared to lipids. Small molecule fluorescent probes allow biomolecule tracking studies with less unfavorable interactions and higher membrane permeability. Still, small-molecule probes generally require the fixation of cells, and there is currently no method to distinguish subpopulations of lipids. The Chenoweth group reported a novel approach to overcome the barrier of separately tracking molecules in different localizations with the first class of small “photoconvertible” dyes. A photoconvertible fluorophore is particularly useful for signaling lipids as they are involved in multiple pathways simultaneously, and the localization of the molecule often determines the pathway it takes. We develop a novel tracking tool to allow subpopulation live-cell tracking studies in signaling lipids. We validate this tool using cholesterol – alkyne – CPX (CACPX), which was used to track cholesterol trafficking and show further applications of photoconvertibility.

Live subpopulation lipid signaling tracking with a novel <i>“clickable” </i>photoconvertible small molecule

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ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.

Live subpopulation lipid signaling tracking with a novel “clickable” photoconvertible small molecule