Watching the Protein Tango

A new technique helps researchers visualize molecules moving in close to real time.

A new microscope has allowed researchers to watch molecules move within a cell on a millisecond-by-millisecond time scale for the first time. The novel method, which combines two preëxisting microscopic techniques, opens a window onto cellular processes that had previously been undetectable, unveiling molecular activity within a cell at a much finer level than ever before possible.

“This allows us to look at interactions of molecules, and their mobility,” says Malte Wachsmuth, a cell biophysicist at the European Molecular Biology Laboratory in Heidelberg, Germany, who helped develop the new microscope. Current microscopy techniques can home in on a single spot within a cell, but they can miss vital information when the focus moves from one spot to another. “A typical protein might spend one to two milliseconds in such a spot,” Wachsmuth says. “Molecules are quite mobile, diffusing all around, and it’s a very fast process. A lot can happen in a few tens of milliseconds.”

The technique developed by Wachsmuth and his colleagues allows them to analyze proteins and other molecules inside an entire cell, all at once, as they move about. It combines light-sheet microscopy, which illuminates just a thin plane of an object, and single-molecule spectroscopy, which can track movements of individual molecules. The result offers both high sensitivity and fast processing time.

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