The new microscope enables scientists to watch and measure fast-moving molecules. |
Researchers
can now watch molecules move in living cells, literally millisecond by
millisecond, thanks to a new microscope developed by scientists at the
European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany.
Published online today in Nature Biotechnology, the new technique
provides insights into processes that were so far invisible.
By
combining light-sheet microscopy and single molecule spectroscopy, the
new microscope can record the fluorescence of every pixel within view,
and take snapshots at intervals of less than one millisecond. 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 only observe at most a
few isolated spots in a sample at a time.
“It’s
really visual biochemistry,” says Malte Wachsmuth, who developed the
microscope at EMBL. “We can follow fluorescently-tagged molecules in
whole live cells, in 3D, 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 forms
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 they used the new microscope to
measure the interaction between chromatin and a protein called HP1-?,
the EMBL scientists made an intriguing discovery.
“In
some areas that look like euchromatin, HP1-? behaves as it would in the
presence of heterochromatin,” says Michael Knop, now at the University
of Heidelberg, Germany. “This suggests that chromatin may also exist in
an intermediate state between hetero- and euchromatin, which was not
observable before in living cells.”
Layout of the new microscope. |
By
providing a tool to watch molecules that move very fast, the scientists
believe this new microscope will help to investigate processes ranging
from the role of growth hormones in cancer to the regulation of cell
division and signalling and the patterning of tissue development in the
embryo.
Quantitative fluorescence imaging of protein diffusion and interaction in living cells
