The cell membrane is the physical barrier separating a cell from its surroundings. It is selectively permeable to water, sugars and other nutritive substances and molecules, and controls what enters and leaves a cell. For it to work properly, the membrane surface is lined with special proteins whose function depends on their position and how they interact with other molecules in the cellular environment.

It is no easy task to study the structure of cell membranes and how they evolve and move at the same time. The membranes are very thin, around just 5 nm across, which makes them extremely difficult to study with conventional microscopy techniques that involve fluorescent markers that can be bigger than a membrane protein itself.

Simon Scheuring and colleagues of Aix-Marseille Université at Inserm (the French National Institute of Health and Medical Research) have now employed high-speed atomic force microscopy (AFM) to look at how membrane proteins organize themselves and how these molecules move. The technique, described in Nature Nanotechnology, is similar to traditional AFM except that the microscope cantilever is much shorter and the piezo scanner much smaller and faster. "All the elements have been miniaturized in fact and the electronics adapted to match the increased speed of the microscope," explained Scheuring.

Using their technique, the researchers succeeded in filming unlabelled proteins in the outer cell membranes of the bacteria Escherichia coli with unprecedented resolution. They also determined how the proteins interacted with one another and other molecules as they moved. "We were not only able to see one protein molecule but all of the molecules in a given membrane," Scheuring told "This is different to fluorescence microscopy where you only observe the protein that has been tagged."

The team also found that if a protein molecule has space to move, then it moves very fast. However, if the space around the protein is crowded with other molecules, then the protein interacts with these. Such interactions are often crucial to the correct function of these proteins, says Scheuring.

The work could lead to applications in medicine, he adds. "Protein membranes are very important targets for a number of drugs so understanding how the membranes interact with these and other molecules will be crucial in further developing and improving these medicines."

The team says that it is now busy looking at more complex biological membranes using its technique.