Chemical tags for living cells

New fluorescent labels can help distinguish between types of cell.

Is this a healthy cell or part of a dangerous tumour? Distinguishing between cells or cell types is a fundamental problem in medical diagnosis and therapy. Now, US chemists have developed a way of telling cells apart by using natural carbohydrate metabolism to introduce non-natural chemicals that certain cells will display on their surface, even in the living animal.

The team, led by Carolyn Bertozzi at the University of California,US, and the Lawrence Berkeley National Laboratory, US, used a chemical tagging system they had developed earlier, called the Staudinger ligation. This is based on an organic azide compound which reacts with a fluorescently labelled phosphine to form a stable amide that can be easily localised by fluorescence microscopy. As the biosynthetic pathways for the synthesis of cell surface glycans are remarkably tolerant of non-natural substrates, the researchers were able to introduce the azide function in the shape of a mannose derivative.

Going through the metabolism, the azide literally resurfaced in the shape of an N-alpha-azidoacetyl sialic acid within the membrane glycoconjugates. Feeding the azide compound to mice resulted in presentation of the azide function on the surface of splenocytes, a cell type naturally rich in sialosides.

Glycosylation patterns of cell surfaces are notoriously complex and challenging for current analytical methods.

By introducing a chemical tag that is easy to monitor and could potentially be used in similar ways to specifically label different kinds of surface markers, Bertozzi has made it easier to distinguish between cell types, and possibly even between individual cells.

Ten years ago, labelling genes or cells with green fluorescent protein (GFP) revolutionised molecular biology. Azide-modified sugars provide a similarly useful label that one can even swallow like a pill, and it may have a similar impact.

Michael Gross