By Mary-Russell Roberson

People with cystic fibrosis experience airway issues daily. Their bodies produce sticky mucus that doesn’t move easily. As a result, it can build up in their airways, leading to infections, lung damage, serious breathing problems, and even death.

But recent discoveries from the lab of Michael Rubinstein, PhD, the Aleksander S. Vesic Distinguished Professor, could one day allow cystic fibrosis patients to breathe easier and perhaps live longer.

Rubinstein studies soft matter, which is a large class of natural and synthetic materials that can be deformed or manipulated, such as mucus, DNA, rubber, gels, liquid crystals, fabric, and plastics. He searches for the physical principles that govern individual types of soft matter, then looks for ways to apply those principles to other types of soft matter. “These are completely different things,” he says, “but their properties are based on similar principles.”

For example, the same principle that makes a tire less likely to skid could help make diapers more absorbent. In addition, understanding how soft matter works in our bodies can inform synthetic material design and vice versa. If you’re looking to make rubber super elastic, which means making sure its long molecules don’t get entangled, look to nature. “Nature has solved it,” Rubinstein says, “because when DNA separates, it doesn’t entangle.”

Rubinstein has joint appointments in engineering, physics, and chemistry, and he draws on all those fields and more to crack the secrets of soft matter. In the past several years, he has branched out into biology and medicine to illuminate the physical properties of mucus and the tiny hair-like structures called cilia that line our airways.

“Michael is a phenomenon,” says Richard Boucher, MD, the director of the Marsico Lung Institute and UNC Cystic Fibrosis Center at the University of North Carolina at Chapel Hill. “He’s got this amazing ability to see things in physical terms and quantitate them mathematically yet understand the complexity and messiness of biology.”

His most recent discovery is about the nature of mucus itself. “What people thought mucus is,” Rubinstein says, “is completely wrong.” It turns out that the properties we ascribe to mucus are not present throughout, but reside only in the top layer. The surface layer is elastic and viscous, while the rest of the mucus behaves like water. “It’s a big breakthrough,” he says. “We discovered it by chance.”

One of Rubinstein’s PhD students, Qishun Tang, made the discovery while measuring the viscosity of mucus. Rubinstein suggested he compare measurements made with different devices, and Tang discovered that the viscosity changed depending on the size of the device. That didn’t make sense if mucus is uniform. “We realized it all comes from this very, very thin layer and the bulk of the mucus wasn’t contributing [to the viscosity],” Rubinstein says.

Rubinstein and the members of his lab are continuing to probe the properties of the viscous layer. Intriguingly, it is made of the same kinds of molecules as the rest of the mucus, but they behave differently, sticking together to form a skin, much like the skin on top of pudding.

Rubinstein’s discoveries about the physical properties of mucus and the cilia in our airways provide targets for researchers looking for medicines to treat diseases like cystic fibrosis and chronic obstructive pulmonary disease (COPD). Boucher says Rubinstein’s work has helped to “revolutionize” the fields of cystic fibrosis and COPD research.

Rubinstein himself is working on an inhalable drug to induce sticky mucus to flow. “We have found surfactants that do make it flow,” he says, “but we have to make sure those surfactants are benign for us.”

In addition to helping people with cystic fibrosis or COPD, Rubinstein’s findings could lead to treatments for less serious conditions, like colds and seasonal allergies. “A very small part of the population has cystic fibrosis,” Rubinstein says, “but a lot of other people have mucus they would like to be able to clear.”

In addition to doing his own research, Rubinstein is committed to fostering the multidisciplinary collaborations necessary in the field of soft matter. He and others have established the Soft Matter Association of the Americas to connect different scientists and professional organizations through yearly international conferences.

“Scientists working in all different disciplines – medicine, physics, chemistry, materials science – are working with similar materials but don’t know about each other’s work,” he says. “That’s why connecting them together will help tremendously to advance the field.”