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Analytical Chemistry

Single Glycoproteins Caught In Motion

Fluorescence-labeling technique could aid understanding of cancer growth

by Stu Borman
January 5, 2015 | A version of this story appeared in Volume 93, Issue 1

Scientists have devised a way to track the movement of single glycoprotein molecules on surfaces of living cancer cells and on microfibrils that connect cells. The work could aid understanding of the role membrane glycans play in cancer growth and spread. Up to now, glycan motions have generally been studied by taking averages of the behavior of many sugar molecules. Peng Wu and Ben Ovryn of Albert Einstein College of Medicine, in New York City, and coworkers now report a fluorescence-based method that visualizes motions of single glycoproteins (Angew. Chem. Int. Ed. 2014, DOI: 10.1002/anie.201407976). The approach monitors the fluorescence of dye molecules linked by click chemistry to azide-tagged O-linked glycans or alkyne-tagged N-linked glycans on live metastatic cancer cells. The study reveals that the glycans exhibit “constrained diffusion”—that is, they diffuse only one-third to one-half as fast as those on nonmetastatic cells. Wu, Ovryn, and coworkers also used the approach to take STORM (stochastic optical reconstruction microscopy) images of glycans on membrane microfibrils in live cancer cells.

 
A reaction scheme showing N-linked and O-linked glycoprotein diffusion.
Credit: Adapted from Angew. Chem. Int. Ed.
By attaching fluorescent groups to N- or O-linked glycans, researchers can now monitor the movements of cell-surface glycoproteins on a single-molecule level.

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