Electron microscopes allow cell biologists to visualize the tiniest of cellular features, but struggle to locate rare features or events. Fluorescence light microscopy (FM) is well suited to this task, but its resolution is low. So Marko Kaksonen, John Briggs and their colleagues at the European Molecular Biology Laboratory in Heidelberg, Germany, combined the two modalities to image rare features with a precision of less than 100 nanometres.
Using yeast cells, the authors show that most signals from fluorescently tagged proteins are still detectable even after the cells have been embedded in resin and sectioned for electron microscopy (EM). To correlate signals from FM and EM, the researchers introduced small microspheres visible in both modalities into the samples. From these, they were able to map features found in FM to images obtained with EM.
The team used the technique to image single HIV particles on mammalian cell surfaces.
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Cell biology: Best of two microscopes. Nature 469, 134–135 (2011). https://doi.org/10.1038/469134d
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DOI: https://doi.org/10.1038/469134d
