DNA imaged with electron microscope for the first time

It's the most famous corkscrew in history. Now an electron microscope has captured the famous Watson-Crick double helix in all its glory, by imaging threads of DNA resting on a silicon bed of nails. The technique will let researchers see how proteins, RNA and other biomolecules interact with DNA.

The structure of DNA was originally discovered using X-ray crystallography. This involves X-rays scattering off atoms in crystallised arrays of DNA to form a complex pattern of dots on photographic film. Interpreting the images requires complex mathematics to figure out what crystal structure could give rise to the observed patterns.

The new images are much more obvious, as they are a direct picture of the DNA strands, albeit seen with electrons rather than X-ray photons. The trick used by Enzo di Fabrizio at the University of Genoa, Italy, and his team was to snag DNA threads out of a dilute solution and lay them on a bed of nanoscopic silicon pillars.

The team developed a pattern of pillars that is extremely water-repellent, causing the moisture to evaporate quickly and leave behind strands of DNA stretched out and ready to view. The team also drilled tiny holes in the base of the nanopillar bed, through which they shone beams of electrons to make their high-resolution images. The results reveal the corkscrew thread of the DNA double helix, clearly visible. With this technique, researchers should be able to see how single molecules of DNA interact with other biomolecules.

DNA cords

But at present, the method only works with "cords" of DNA made up of six molecules wrapped around an seventh acting as a core. That's because the electron energies are high enough to break up a single DNA molecule.

Using more sensitive detectors that can respond to lower-energy electrons should soon allow the team to see individual double helices, and even unwound single strands of DNA. "With improved sample preparation and better imaging resolution, we could directly observe DNA at the level of single bases," says di Fabrizio.

Earlier this year a University College London team led by Bart Hoogenboom felt their way along individual strands of DNA using the Braille-like technique of atomic-force microscopy (doi.org/jvc). Like the Italian team, they were able to detect the twisting groove that separates the twin strands of the double helix.

Journal reference: Nanoletters, doi.org/jt3

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