Single-Cell Metabolism

A new assay allows scientists to analyze the metabolism of glycosphingolipids in single cells. The method could help biologists examine cell-to-cell diversity and metabolic regulation of these cell-surface molecules.

Glycosphingolipids are heterogeneous molecules consisting of a saccharide head and a lipid tail. One type of these molecules, called gangliosides (shown), has up to four sialic acids attached to the saccharide head and a long-chain fatty acid attached to the sphingosine lipid tail. Gangliosides make up a large fraction of the outer membrane of neurons. Diseases such as Tay-Sachs are associated with problems in ganglioside metabolism.

By replacing gangliosides??? fatty-acid side chain with the fluorescent dye tetramethylrhodamine, a team led by chemistry professor Norman J. Dovichi of the University of Washington, Seattle, analyzed ganglioside metabolism in 54 individual cultured pituitary tumor cells using capillary electrophoresis and laser-induced fluorescence (Anal. Chem., DOI: 10.1021/ac070716d). They can detect at the low zeptomole (10^???21) level all metabolites that retain the dye.