Visual Biochemistry Tracks Molecules in Action

With more precision than ever, researchers can watch molecules move inside living cells, thanks to a new microscope developed at the European Molecular Biology Laboratory (EMBL).

By combining light-sheet microscopy and single-molecule spectroscopy, the novel microscope can record the fluorescence of every pixel within view and take snapshots at <1-ms intervals. With it, scientists can watch and measure very fast processes, such as the way molecules diffuse across a whole sample, even one containing several cells. This is a considerable step up from previous techniques, based on confocal microscopy, in which researchers could observe at most only a few isolated spots in a sample.

A microscope developed by German researchers enables imaging and measurement of fast-moving molecules. (Image: EMBL, H. Neves)

“It’s really visual biochemistry,” said Malte Wachsmuth, who developed the microscope. “We can follow fluorescently tagged molecules in whole live cells, in 3-D, and see how their biochemical properties, like interaction rates and binding affinities, vary throughout the cell.”

Until now, chromatin — the combination of DNA, RNA and proteins that form chromosomes — had been observed in two states: wound tightly together, with most of its DNA inaccessible to the cell’s gene-reading machinery, in which case it is called heterochromatin; or loosely packed and easily readable, called euchromatin. But when Wachsmuth and his team used their microscope to measure the interaction between chromatin and the protein HP1-a, they made an intriguing discovery.

“In some areas that look like euchromatin, HP1-a behaves as it would in the presence of heterochromatin,” said Michael Knop, now at the University of Heidelberg. “This suggests that chromatin may also exist in an intermediate state between hetero- and euchromatin, which was not observable before in living cells.”

By providing a tool to watch molecules that move very fast, the scientists believe the microscope will help investigate processes ranging from the role of growth hormones in cancer to the regulation of cell division and signaling and the patterning of tissue development in the embryo.

For more information, visit: www.embl.de