Going nano to see viruses 3-D

'Technical tour de force' is first step to seeing proteins in 3-D

Physicists have created an MRI-like machine capable of making three-dimensional scans of single virus particles — a resolution 100 million times higher than previously possible.

The achievement is a step toward imaging individual proteins, the knotted molecules that assemble to form viruses and that play a central role in the chemistry of all life.

“Our long-term dream is to have a technique that could look at the 3-D structure of molecules in your body such as proteins,” says Daniel Rugar, a physicist with IBM Research at Almaden Research Center in San Jose, Calif. Currently, finding proteins’ 3-D shapes requires first crystallizing the proteins, a difficult and time-consuming step that hinders protein research. Rugar’s MRI-like technique, reported online January 12 in Proceedings of the National Academy of Sciences, might someday image individual particles without the need for crystallization.

Like MRI machines used in hospitals, the new technique depends on a phenomenon called nuclear magnetic resonance, or NMR — the ability of a strong magnetic field to make atoms’ magnetic spin axes line up like little compasses pointing north. However, the new method differs from hospital MRI machines in how it senses this effect.

In traditional MRI, an antenna detects wobbles in the atoms’ magnetic spin axes. Rugar’s nanoscale MRI instead senses the mechanical push and pull of the viruses’ atoms on a microscopic cantilever arm. The researchers placed the virus particles on the tip of the arm and positioned the tip close to a strong, tiny, fixed magnet. As the magnetic spin axes of the hydrogen atoms in the viruses flipped up and down, the atoms were alternately attracted to and repelled by the fixed magnet, thus creating the pushing and pulling on the arm. The strength of these forces indicated how many hydrogen atoms were at a given spot in the virus, and moving the tip around built up a 3-D representation of the virus shape.

“It’s pretty much a technical tour de force,” comments J. Michael Tyszka, an applied physicist and associate director of the Caltech Brain Imaging Center in Pasadena, Calif. “It could be very influential if they could get unique data that you can’t get with scanning electron microscopes.”

In the study, Rugar’s team confirmed the shape of the virus depicted in the MRI images by checking the inferred against images taken with an electron microscope. However, even electron microscopes can’t image individual proteins. Other techniques, such as atomic force microscopy, can image individual atoms on the surface of an object, but those methods can’t produce a 3-D image of the entire object and its interior, which the new nanoscale MRI can.

Because the object being scanned must be placed on the tip of a microscopic cantilever, the new technique couldn’t be used for imaging people or other large objects at very high resolution.

Rugar says improving the resolution enough to image proteins will require using a stronger fixed magnet and detecting smaller push and pull forces on the cantilever.

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