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Capturing Protein Interactions

Freezing and slicing gives a snapshot of life inside cells.
February 19, 2008

Scientists can now see how proteins organize and interact, thanks to the tech­nology that created this image of skin tissue. The technique reveals the structure of proteins and the relationships among them in unprece­dented detail, providing information that’s vital for understanding disease and cell functions. “When you see the proteins, you immediately also see … how they interact in an undisturbed environment,” says Achilleas Frangakis, the biologist who led the research at the European Molecular ­Biology Laboratory in ­Heidelberg, Germany. “At this resolution, the cell is essentially an uncharted terri­tory.”

This 3-D reconstruction reveals details such as the nucleus (blue) and mitochondria (purple) of a skin cell, as well as hairlike proteins (brown, at bottom) that link cells to each other.

The research group froze cells to -193 ºC by plunging them into liquid nitrogen, sliced them into 50-nanometer­-thick sections, and illuminated the slices with a beam of electrons. Software refined the resulting electron tomography images into virtual slices that were even thinner–as little as half a nanometer thick. Combinations of such slices enable 3-D viewing, too.

The imaging technique, called cryo-­electron tomography, had previously been used on smaller, simpler cells, such as bacteria. But coupled with the slicing technique, cryosectioning, it can work on almost any cell and is “truly a first,” says Grant Jensen, a biologist at Caltech who specializes in cryo-electron tomography.

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