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Peering into Cellular Worlds

By Emily Singer

Although the two methods described here so far provide a way to look at molecules inside cells, they can’t image anything smaller than about 300 nanometers. The ability to distinguish, say, a pair of five-nanometer proteins would open a new window onto the inner workings of cells, says Xiaowei Zhuang of Harvard University. Zhuang labels proteins with specially designed fluorescent tags that can be quickly turned on and off with light. She then activates only a few sparsely placed tags at a time. These are clearly separate from each other under an optical microscope, allowing her to map their precise locations. The process is repeated again and again, each time capturing the location of a few tags. Then the images are combined to create a cohesive picture. “Having such a high-­resolution technique allows interactions among molecules to be much better revealed in a cell,” says Zhuang.

In this image, a circular filament made of DNA-binding proteins is shown as depicted both by conventional wide-field microscopy--a yellowish blob--and by Zhuang’s technique, which reveals a crisp ring of peaks, indicating the location of tag molecules.