by Anil Ananthaswamy

In Prey, Michael Crichton's tale of nanotech gone awry, a swarm of light-sensitive nanoparticles swim through a human body, creating the ultimate medical imaging system.

In the real world, biochemists are hoping to go one step further, deploying viruses as "nano-cameras" to get a unique picture of what goes on inside living cells and a greater understanding of how viruses themselves work.

Researchers currently study living cells using a technique called Raman spectroscopy. When laser light bounces off some materials, most of the scattered light has the same wavelength as the incident light. But a fraction called the Raman spectrum has an altered wavelength due to the characteristic vibration of some molecules in the material.

This allows researchers to map the coarser features of a cell, such as its nucleus. But Raman spectra are very weak. Introducing gold nanoparticles into cells enhances the Raman signal more than fivefold, because electrons on the surface of the nanoparticle interact with and reinforce the scattered light.

Unfortunately, the cell treats gold nanoparticles as foreign bodies and quickly clears them out. But viruses are already able to avoid ejection. So Dragnea and his team decided to use them as Trojan horses to smuggle the particles into living cells.

Viral shell

To get the gold inside a virus, the researchers took a pathogen that infects barley, called the brome mosaic virus, and put it in an alkaline solution. This breaks down the viral shell into its constituent amino acids.

Then they allowed the virus to reassemble itself by lowering the solution's pH. When this was done in the presence of gold nanoparticles just five nanometres in diameter, many of the reassembled shells had gold instead of viral RNA inside them.

When a green laser was shone on the virus as it floated around in a culture medium designed to mimic the cellular cytoplasm, certain amino acids on the viral shell emitted characteristic Raman signals, boosted by the gold nanoparticle.

"This allows us to see a single virus at a time [under the microscope]," says Dragnea. Until now, biologists have mainly studied populations of viruses. Dragnea now plans to try the technique on a barley plant cell.

If it works, virologist Lynn Enquist of Princeton University says it will be a breakthrough. "The only way we could look at individual viruses was in fixed preparations, using electron microscopy," he says. "Imaging individual viruses in living cells is powerful technology."

The virus can also map the cell's chemistry, because Raman signals vary depending on the pH or ionic strength of the virus's environment. The maps will have an astonishing resolution of about 30 nanometres - the diameter of the virus.