A self-guided fluorescent probe can reveal minuscule amounts of enzymes hidden in the farthest reaches of a living cell.
The adaptable probe — designed by Yamuna Krishnan and her colleagues at the University of Chicago in Illinois — includes both ‘sensing’ and ‘targeting’ modules. In the team’s prototype probe, the sensor glows when it encounters a chemical reaction called a disulfide exchange. The targeting module consists of a particular DNA segment; this guides the probe to cell structures known as endosomes that function as internal cargo compartments.
When added to the cells of Caenorhabditis elegans worms, the probe ferreted out two enzymes that catalyse disulfide exchange inside endosomes. The researchers deployed the probe in worms infected with the diphtheria bacterium (Corynebacterium diphtheria) and found that the bacterium hijacks one of these enzymes to produce its powerful toxin.
The probe’s sensing and targeting modules can be customized to hunt for various enzymes in a vast assortment of cellular structures, the scientists say.