Nature Nanotechnology

It's one thing when a nature videographer captures a fast-moving creature in the wild and has to put up with the background images being blurry while the focus stays fixed on the object of interest. It's quite another when scientists are trying to sneak a peek at a virus as it interacts with the surface of a cell and want to focus on the virus and the cell simultaneously.

Now researchers at Princeton University say they've captured unprecedented 3D footage of a virus-like particle as it appears to try to enter a cell. To keep everything in focus they used two cameras -- one that followed the virus-like nanoparticle, and the other that used laser-scanning microscopy to take multiple images in a slightly different focal plane and thus remain focused on the cell and its nearby environment.

Writing this week in the journal Nature Nanotechnology, they say their approach could ultimately help scientists learn more about virus-cell interactions to both prevent viral infections (which alone would be a major accomplishment) and deliver antiviral drugs in an extremely targeted manner using nanoparticles that are roughly the same size as a virus.

"The challenge in imaging these events is that viruses and nanoparticles are small and fast, while cells are relatively large and immobile," first author Kevin Welsher, a postdoctoral researcher in Princeton's chemistry department, said in a news release. "That has made it very hard to capture these interactions."

After filming with two cameras, Welsher and adviser Haw Yang stitched the two images together to create what they say is the most detailed footage of a nano-sized particle to date. (A technique called electron microscopy can also image objects of this size at roughly this resolution, but the approach is limited to 2D and only works on dead cells.)

And because the virus-like particle bumped around along the cell's surface, the researchers say they might be able to use this approach to get a detailed map of the contours of the cell's surface much in the way a blind person might use his or her fingers to learn about objects. "Following the motion of the particle allowed us to trace very fine structures with a precision of about 10 nanometers, which typically is only available with an electron microscope," Welsher said in the release.

By measuring changes in the particle's speed, they were even able to infer the viscosity (similar to thickness) of the environment immediately around the cell.

The 3D footage could ultimately shed light on the most basic questions about how viruses and cells interact, which could in turn help scientists prevent viral infection in the first place rather than focus on treatment and the aftermath.

Check out the footage below. It should be noted that this is a 100-nanometer-wide particle (made by the researchers themselves to closely resemble a virus) that has been let loose in a dish containing skin cells. To make the particle, they coated a tiny polystyrene ball with light-emitting quantum dots and studded with Tat peptides, which are protein segments derived from the HIV-1 virus that help the particle navigate toward a cell.