January 13, 2009

A Breakthrough in Imaging: Seeing a Virus in Three Dimensions
By JOHN MARKOFF
NY Times

http://www.nytimes.com/2009/01/13/science/13mri.html?ref=technology&pagewanted=print


For the first time, researchers at an I.B.M. laboratory have captured a 
three-dimensional image of a virus.

The technique used by the I.B.M. scientists has some similarity to 
magnetic resonance imaging, or M.R.I., now routinely used by physicians 
to peer inside the human body. But the results were 100 million times 
better in terms of resolution with the new technique, magnetic resonance 
force microscopy, or M.R.F.M. The team of researchers, based at the 
computer maker’s Almaden Research Center in San Jose, Calif., reports in 
the The Proceedings of the National Academy of Sciences that they have 
captured a 3-D image of a tobacco mosaic virus with a spatial resolution 
down to four nanometers.

Techniques like atomic force and scanning tunneling microscopes have 
provided images of individual atoms. (An atom is about one-tenth of a 
nanometer in diameter). But these techniques are more destructive of 
biological samples because they send a stream of electrons at the target 
in order to get an image. And these microscopes cannot peer beneath the 
surface of the Lilliputian structures. The researchers said that many of 
their ideas had evolved from earlier work on atomic force microscopes. 
“The one thing that has always intrigued me, is, can we take the same 
idea and do it in three dimensions?” said Daniel Rugar, an I.B.M. 
physicist who helped design the first M.R.F. microscope in 1993. “We’d 
like to be able to take pictures of atomic structures like molecules. 
That’s been our motivation.”

The development of M.R.F.M. as a three-dimensional microscope actually 
began in 1991 with publication of a speculative paper by a theoretical 
physicist, John A. Sidles, who was then searching for new tools to help 
design drugs to combat the AIDS virus. After reading about atomic force 
microscope research at I.B.M., Dr. Sidles, who is a professor of 
orthopedics at the University of Washington School of Medicine, called 
Dr. Rugar and proposed a related tool that measured minute magnetic 
fields to construct images of biological structures.

“He realized that many of the diseases that they see are 
molecular-based,” Dr. Rugar said. In research in 2004, Dr. Rugar and 
others were able to make an image of a single electron with the new 
technique. The new achievement is the dimensionality of the image.

Magnetic resonance force microscopy employs an ultrasmall cantilever arm 
as a platform for specimens that are then moved in and out of proximity 
to a tiny magnet. At extremely low temperatures the researchers are able 
to measure the effect of a magnetic field on the protons in the hydrogen 
atoms found in the virus.

By repeatedly flipping the magnetic field, the researchers are able to 
cause a minute vibration in the cantilever arm which can then be 
measured by a laser beam. By moving the virus through the magnetic field 
it is possible to build up a 3-D image from many two-dimensional samples.

The researchers said they believed the tool would be of interest to 
structural biologists who are trying to unravel the structure and the 
interactions of proteins.

It would be particularly useful for biological samples that cannot be 
crystallized for X-ray analysis. Although the structure of DNA molecules 
has already been characterized by other means, it will be possible to 
use the system both to look at the components that make up the basic DNA 
structure as well as to make images of interactions among biomolecules, 
Dr. Rugar said.

-- 
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George Antunes, Political Science Dept
University of Houston; Houston, TX 77204 
Voice: 713-743-3923  Fax: 713-743-3927
Mail: antunes at uh dot edu

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