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Extending the reach of expansion microscopy

Click chemistry makes superresolution imaging applicable to more types of biomolecules

by Celia Henry Arnaud
December 17, 2020 | A version of this story appeared in Volume 98, Issue 48


Image obtained by click expansion microscopy of monkey fibroblast cells with fluorescently labeled lipids.
Credit: Nat. Methods
Researchers used click expansion microscopy to obtain this fluorescence image of lipids (magenta) in monkey fibroblast cells. The mitochondrial matrix (green) and mitochondrial membrane (red) are also shown.

Expansion microscopy enables superresolution imaging with conventional fluorescence microscopes. In expansion microscopy, biological samples are embedded in and anchored to a hydrogel. When the hydrogel is stretched, individual features move away from one another while staying in the same relative position, making them easier to distinguish. Until now, the method has been limited mostly to proteins and nucleic acids. Xing Chen and coworkers of Peking University have combined click chemistry with expansion microscopy (click-ExM) in a method that works with all kinds of biomolecules (Nat. Methods 2020, DOI: 10.1038/s41592-020-01005-2). In click-ExM, biomolecules are metabolically labeled or genetically encoded with an alkyne or azide group, which then reacts with azide- or alkyne-labeled biotin. Fluorescent tags labeled with streptavidin are added to the sample. The streptavidin reacts with the biotin and with linkers to anchor the biomolecules to the hydrogel. By using 18 clickable labels, the researchers used click-ExM to image various biomolecules, including nucleic acids, proteins, lipids, glycans, and small molecules, in cells and tissues.


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