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WITH the right lighting and atmosphere, it is possible to take snapshots of
proteins during their most intimate moments鈥攁s they interact in the
processes of life. But like all still photos, this records just a single moment,
frozen in time. Now a team of researchers has found a way to make movies of two
proteins interacting.

Researchers typically use a scanning electron microscope to get pictures of
individual proteins, but you can only do this in a vacuum. Unfortunately,
biology doesn鈥檛 take place in a vacuum, says Mario Viani of the University of
California in Santa Barbara. So he and his colleagues captured real-time images
of two proteins doing their stuff by using a modified atomic force microscope
(AFM), which has the same high resolution as a scanning electron microscope but
can work in liquid.

The AFM uses a needle-fine probe on the end of a cantilever arm to 鈥渇eel鈥� the
surface features of a sample stuck to a glass substrate. As the tip is dragged
over the surface and moves up and down, the cantilever bends in response. A
laser records these tiny movements and a computer turns them into an image on a
screen.

But standard AFM probes, at 30 micrometres across, were too big to study
single proteins at work, so Viani designed one just 5 micrometres wide鈥攐ne
tenth the diameter of a human hair. This tip can detect smaller forces and move
up and down with higher frequency, so it can record the rapid movements of
interacting molecules.

To test their fast-action AFM, Viani and his team used bacterial proteins
called Gro chaperonins as a model. GroEL binds to its partner GroES to form a
complex that repairs misfolded proteins. In the experiment, the researchers
anchored GroEL to a glass substrate in solution and scanned the surface. The
scan showed a flat, even line. After adding GroES to the solution, certain
regions of the line had raised areas or bumps. 鈥淲e are able to `see鈥� the two
proteins interact,鈥� explains Viani.

With the AFM, you can vary what goes into the solution and instantly watch
how proteins react. 鈥淚 am sure there are many exciting things to come from
single-molecule studies,鈥� says Viani.