A biofilm epic in the making

There are a lot of ways to cut film, as many cinemas and directors can attest. But biofilms—which settle on numerous surfaces, including skin—can contain harmful bacteria and get in the way of healing wounds.

two men and one woman in a lab — Mason researchers Jeffrey Moran, Rémi Veneziano, and Monique van Hoek, Photo by Evan Cantwell/Creative Services

Assistant Professors Jeffrey Moran in the Department of Mechanical Engineering and Rémi Veneziano in the Department of Bioengineering at George Mason have a shared interest in using nanotechnology for medical applications, as well as a shared history. Both worked as postdocs at the Massachusetts Institute of Technology, but it wasn’t until they started working at Mason that their paths crossed. Partnering up with Professor Monique van Hoek, a microbiologist in the School of Systems Biology at George Mason, they applied for and recently won the National Institute of Biomedical Imaging and Bioengineering (NIBIB) R21 Trailblazer award.

Through the award funds, the team will use their backgrounds and spend about three years developing a brand-new technology that dissolves harmful biofilms, without harsh removal methods.

“You can think of a biofilm as a ‘city for microbes.’ Biofilms are functional communities of microorganisms, such as bacteria, encased in a slime-like matrix,” says Moran. “Bacterial biofilms often grow on catheters, IVs, open wounds, burn injuries, and more, and they play a major role in many hospital infections. We’re going to develop a safe and effective method to remove topical biofilms that doesn’t get in the way of the body’s natural healing process.”

Some biofilms are relatively benign, and many folks have them on the surfaces of their teeth. But harmful biofilms can develop throughout the body for many reasons, like on the skin surface as a result of trauma, and cause potentially fatal infections.

Moran’s primary research focus is on “nanoswimmers"—tiny particles that propel themselves in liquids or biological media. Many researchers are developing them to use in the body, to deliver therapeutic payloads (like antibiotics) to hard-to-reach locations.

“One major challenge with bacterial biofilms is how to make them disassemble," says van Hoek. “There are three major parts to a biofilm—DNA, protein, and complex sugars. Destroying any one of these three things often leads to biofilm collapse. My idea was to use a sugar cleaving enzyme to attack the sugars in the biofilm, and to attach this enzyme to the front of the nanoswimmers so that they can drill deep into the biofilm.”

“What we’re trying to do is develop self-propelled particles that penetrate deep into the thick matrix of the biofilm, dissolving it and also serving as a carrier to deliver antibiotics at the same time,” says Veneziano.

To manufacture the self-propelled particles, the team is relying on Veneziano’s specialty: DNA origami, which is a method that involves precisely assembling DNA molecules into tiny two- and three-dimensional shapes.

“With DNA origami, you have the ability to produce tailor-made particles with phenomenal control over the size, shape, and the cargo they carry," says Veneziano. "DNA origami’s versatility will enable the particles to be decorated with various cargoes, such as antibiotics or enzymes that dissolve the biofilm matrix, leaving the bacteria vulnerable to conventional antibiotic treatments.”

Although using enzymes to dissolve the biofilms isn’t new, attaching them onto DNA origami nanoparticles is, which is the trailblazing path Veneziano, van Hoek and Moran will follow.

“It all started with a ‘what if we tried this?’ type of conversation. We bounced ideas off each other, talking about ways we might make DNA nanoparticles swim, and how that capability might be useful in certain medical situations. That back-and-forth eventually led to this award,” says Moran. “We’re excited to get started.”

The R21 Trailblazer Award is an opportunity for new and early-stage investigators to pursue research programs of high interest to the NIBIB at the interface of the life sciences with engineering and the physical sciences. A Trailblazer project may be exploratory, developmental, proof of concept, or high risk/high impact, and may be technology design-directed, discovery-driven, or hypothesis-driven.