A miniaturized cantilever tracing the contours of the DNA double helix, with its deflection detected by laser optics (not to scale). |
When
Watson and Crick discovered the DNA double helix nearly sixty years
ago, they based their structure on an averaged X-ray diffraction image
of millions of DNA molecules. Though the double helix has become iconic
for our molecular-scale understanding of life, thus far no-one has ever
“seen” the double helix of an individual double-stranded DNA in its
natural environment, i.e, salty water.
Dr. Carl Leung and a team of international collaborators led by Dr. Bart Hoogenboom at
the London Centre for Nanotechnology (LCN) have now done just that. To
visualise DNA, they used a technique called atomic force microscopy
(AFM) that detects the molecules by ‘feeling’ them, as a blind person
would with a cane. Atomic force microscopy is known for its ability to
achieve up to atomic resolution on flat surfaces, but often struggles to
resolve more complex structures such as biological molecules. Imaging
DNA, for instance, is analogous to using a cane to visualize a wriggling
snake: not an easy task!
To
resolve the double helix, the researchers miniaturized the cane (the
“cantilever”) to approximately 10 micrometers length (an eighth of the
width of a human hair) and nanometer-scale thickness. Next, they made it
vibrate at sub-nanometer amplitudes and detected the proximity of the
DNA via minute changes in the resonance frequency of the cantilever.
The
resulting images show the two strands of the double helix twisting
around the central axis of the molecule, in a clockwise, right-handed
fashion, similar to a corkscrew entering a cork. The so-called major
groove is clearly resolved, separating the turns of the double helix, as
well as the minor groove that separates the two strands of the double
helix. This level of detail sets these images apart from all other AFM
measurements on DNA over the past two decades.
Interestingly,
the reported method also enabled the researchers to identify and probe a
surprising form of DNA that has a left-handed structure, as opposed to
the canonical right-handed structure of Watson and Crick . In future
this method could therefore be used to study structural deviations of
the double helix, linked to genetic instability and hereditary disease.
Full details and images have been published in the journal Nano Letters:
Source: London Centre for Nanotechnology
