Matt examining research images

Viruses have vexed scietists ever since they've known about them and caused illness and disease for even longer. The common cold still has no cure, and HIV continues to confound us with its ability to morph and thus resist preventative treatments.

Joining the ranks of the many researchers fighting in the battle against these viral menaces, Matt D'Amato, a graduate student at the University of Wisconsin-Madison, hopes that he can one day help render viruses inactive by altering the surfaces on which they sit. Under the supervision of his advisors, Professors Robert Carpick and Mark Eriksson, this Materials Science graduate student studies the forces that are involved when viruses and surfaces interact. "This [could] give us more information about how viruses invade cells," explains Matt, important for preventing infection.

A schematic of a tobacco mosaic virus particle. The red represents the RNA portion, and the blue the protein coat that encases the genetic material.

Matt dreams that one day his research will help us design surfaces that would inactivate viruses. "We know virus particles can exist in an 'active' state outside of the body (on 'dead' surfaces) for some period of time," he explains. "So by studying them on surfaces - determining what 'state' they are in (say, 'active' or 'inactive'), what their conformation and structure are on the surface, etc., we can begin to learn how to engineer surfaces to make viruses do something desirable, like make them inactive." Imagine a kitchen counter or surgical table that causes viruses to become harmless by freezing them in position, in essence a Medusa surface.

It's also possible that future research by Matt and other nanotechnologists like him could lead to drugs that block viral infections.

The small size of his research subject challenges Matt with an issue common to all nanotechnologists - how to see the extremely tiny. To solve this dilemma, Matt uses an atomic force microscope, or AFM, when he looks at the viruses on a surface. Most people use the electron microscope to study these viral particles, so Matt's approach is novel. "AFM is unique," he explains, "because you can analyze the forces involved [between the virus and the surface] by effectively pushing and pulling on the particles and surface. You couldn't use a light microscope or any other instrument to do this."

The AFM is particularly helpful for Matt's research because of how it works. This special microscope creates an image of a sample by physically interacting with it - by running an extremely fine probe tip over the sample's surface and measuring the tip-surface interactions . As a result, Matt finds the AFM helpful for a variety of reasons. "With this tool I can effectively 'see' what the surface looks like. I can image the virus particles, measure their size and distribution, and see what effects the nanoscale [surface] has on them."

A cartoon diagram of the AFM

Matt points to where he puts the samples

The AFM also allows Matt to test the interaction between viruses and the surface by poking them with the microscope tip. Matt coats a textured surface made out of a plastic called polyurethane with a layer of viruses. The nanoscale hills and valleys on the polyurethane affects the viruses differently than a perfectly flat surface would, and Matt uses the AFM to find out how. By probing the viruses with the AFM tip, Matt can analyze the stiffness of the viruses and the amount of friction between them and the surface.

If scientists can gather this information for a virus, it might result in better drugs, explains Matt. "If you know [about the physical traits of a virus on a surface], it may be good for drug design. Studying these properties of virus particles may go a long way towards our understanding of how they infect cells and perhaps how we can design drugs to block infections."

Close-up of the AFM

Several different views of the patterned surface Matt uses. On the left is a cartoon of the grooves; at the top is a profile of the surface; and the colored image at the bottom is a top view of the surface landscape from the AFM, with the colors corresponding to the adjacent height scale.
Yellow represents a hill, and dark brown a valley.

Before Matt uses the AFM to conduct the probing experiment, he has to prepare the virus and the surface for the microscope. To make certain types of viruses, Matt imitates nature and grows them in cells. "I maintain the cells, infect them with a 'seed' virus, let the virus propagate and multiply through many cells, and collect and purify the virus particles." The result of one of Matt's batches was approximately 100 million infectious particles, which he stores in a liquid to make later steps of his experiment easier.

Matt makes the polyurethane surface with nanoscale canyons by using a pre-patterned template. "It looks like a plowed farm field," says Matt when he describes the result. In the future, he'd also like to try varying the surface by using wider or deeper trenches or a softer material.

The last step before Matt is ready to use the AFM involves placing a droplet of the virus liquid onto the grooved surface. After several hours, the virus particles adsorb onto the surface, fixed in place by an additional layer of proteins and antibodies Matt deposits beforehand in the same manner.

Once the sample is ready, Matt can finally use the AFM to "see" his nanoscale viruses and their interaction with the surface. Eventually, he hopes he can predict what the viruses will do based on what the surface is like. "If you can align nanoscale things," explains Matt, "you can study them more easily."

All this will lead to better control over these nanoscale nuisances that make our lives miserable and, hopefully someday, to surfaces that protect us from our sneezes.

An AFM image of tobacco mosaic virus particles (TMV) on polyurethane with nanoscale hills and valleys. The light-colored, rod-shaped particles are TMV, seen most clearly across the ridges. Some TMV also fills the trenches. The color bar on the right indicates the height scale.
The width of the image is 5 micrometers.