The precedent of studying bacterial architecture dates back to the late 1600s, when the Dutch draper Antonie van Leeuwenhoek first observed the cells through his simple microscope.

“Every time you have a big imaging advance, you have an increase in understanding,” says Caltech's Grant Jensen. Today's researchers have profited from two technological leaps forward. The first, Jensen says, is green fluorescent protein and other tags that can reveal cell structure through fluorescence microscopy. They allow researchers to locate molecules and follow their movements.

The second technique is electron cryotomography, or ECT, a method that researchers have been using to probe bacteria for only a few years. Unlike the two-dimensional projections provided by traditional electron microscopy, ECT can capture three-dimensional images of a whole bacterium to reveal internal nuances.

ECT has another big advantage. Preparation of specimens for conventional electron microscopy includes steps such as dehydration and chemical treatment that obliterate much of the internal detail, Jensen says. In ECT, instead of going through this harsh process, the cells are “fixed” by dunking them in liquid ethane at around minus 190 degrees Celsius.

“You get a sample that is stopped in time,” says Jensen. All the molecules and water in the cell stop moving instantly without forming ice crystals that would destroy everything around them. Even fine details are preserved, allowing scientists to see the nuances of individual large
molecules. —M.L.