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First ever pictures of single proteins thanks to graphene sheet

By Jacob Aron

8 January 2016

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You’d think twice about snapping a selfie if the camera flash was bright enough to burn your skin off. Biologists face a similar problem when studying proteins under the microscope, as modern imaging techniques can destroy the molecules. Now graphene – the ultra-thin form of carbon – has come to the rescue, and delivered the very first pictures of a single protein.

Taking pictures of proteins lets us understand their structure and functions. This is important for treating diseases in which proteins go wrong, such as Alzheimer’s. But imaging methods such as X-ray crystallography or cryo-electron microscopy rely on averaging readings from millions of molecules, giving us a blurry view.

Averaging is needed because illuminating molecules with X-rays or high-energy electrons can damage the protein, meaning you may not get the full picture from a single image, and also because it’s tricky to keep a single molecule in one place long enough to take its picture. Now Jean-Nicolas Longchamp of the University of Zurich, Switzerland, and his colleagues have come up with a way to do just that.

They start by spraying a solution of the proteins on to a sheet of graphene, fixing the proteins in place. Then they place this under an electron holographic microscope, which uses interference patterns between electrons to produce an image.

Handy slide

This kind of instrument relies on low-energy electrons that don’t damage the protein. The snag is that they are also less able to penetrate through to the microscope’s detector. This is where graphene comes in handy. “In optical microscopy you have a glass slide. For our electron microscopy we had to find a substrate thin enough to have the electrons passing through,” says Longchamp.

The team tested their method on a range of protein molecules, all just a few nanometres in size, such as the haemoglobin found in red blood cells. The results agreed well with molecular models derived from X-ray crystallography (see image below), suggesting the images are accurate.

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Now they plan to snap pictures of other molecules that can’t be imaged with existing techniques, and hope eventually to contribute to new medical treatments. “There are some diseases which are related to the wrong structure of certain proteins,” says Longchamp. “In the future, we could image the difference in the structure of a healthy person and a person who has a disease.”

Reference: arxiv.org/abs/1512.08958

(Image credit: Jean-Nicolas Longchamp of the University of Zurich, Switzerland)

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