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For healthy people, mucus is our friend. It traps potential pathogens so we have airways can dispatch nasty bugs before they cause harm to our lungs. Cystic fibrosis (CF) and chronic obstructive pulmonary disorder (COPD), mucus can get too thick and sticky; coughing alone can not clear it. Infections develop, leading to severe chronic disease and early death. Now, for the first time, scientists at the UNC School of Medicine and Duke University are demonstrating why they can not tear mucus apart from the airway lining. And they showed how to make mucus thinner and less sticky so they can become a therapeutic aid.
The discovery, published in the Proceedings of the National Academy of Sciences, helps explain how CF affects the importance of therapies that alter mucus to give immediate relief to people with CF. Combining a host of scientific disciplines from the field of biology to materials science, the researchers found that the most important factors in the study of mucus in airway diseases are COPD and asthma, which affect millions of people in the United States.
Brian Button, PhD, associate professor of biochemistry and biophysics and member of the UNC Cystic Fibrosis Research and Treatment Center at UNC-Chapel Hill.
Senior author Michael Rubinstein, Professor in the Department of Mechanical Engineering and Materials Science at Duke University, said, "We measured the adhesive forces that bind mucus to the airway lining and the cohesive forces that hold mucus together, and identified several agents that promise show. reducing the strength of mucus's adhesive and cohesive interactions. "
In healthy people, mucus is 98 percent water. It lines airways to trap particles, including bacteria and other microbes, before they reach the lungs. Less than 1 percent of ordinary mucus consists of long, sticky, chain-like proteins called mucins, which give mucus its gel-like properties. CF, chronic bronchitis, and other "muco-obstructive" diseases feature mucus dramatically more viscous and elastic than normal, almost gelatin-like because it is loaded with mucins. In CF mucus, for example, the amount of mucins jumps to 10 percent and the amount of water decreases to 79 percent. While CF mucus is still mostly water, mucin viscoelasticity.
Typically, the cough reflex produces high-velocity airflows that tear mucus apart and tear it from the airway lining and at the same time. But scientists have never fully understood why coughing fails to clear mucus in muco-obstructive diseases such as CF. Guided by the theoretical work of Rubinstein, a longtime researcher at UNC-Chapel Hill before joining Duke in 2018, the researchers at UNC developed a sophisticated system for testing the mechanical forces required to dislodge and normal fracture and CF-type mucus.
The scientists first took airway-lining cells from the lungs of transplant patients and cultured them in laboratory dishes. These cells produced their own mucus layer. Button said, "They look like miniature versions of a real airway lining."
Because mucus is a very "soft" gel, the researchers developed a technique to embed small meshes, which firmly binds to the mucus. This mesh is then connected via silk thread to a motor with a force sensor to quantify the force required to pull and tear the mucus. This is one of the adhesive and cohesive forces of mucus. And they could compare these forces in normal mucus and CF mucus.
"We found that the adhesive and cohesive strengths of mucus increase dramatically when the ratio of mucins to water is higher than normal," said Button. "In CF mucus, these strengths exceeded the forces produced by coughing.
The UNC and Duke researchers also used this test to determine the efficacy of CF mucus. One treatment – inhaled saline and hypertonic saline (saltier than water in the body) – increases the water content in mucus to make it thinner. The other types of treatments – so-called "mucolytic" therapies – make mucus less viscous and elastic by chopping up or separating mucin molecules to reduce their ability to stiffen mucus. The team found that both types of therapeutics are reducing the adhesive and cohesive strengths of CF mucus.
"For patients, one of these types of therapy should help," said Button. "But their effects are additive, so it would probably be better to combine these two hypotheses, just for the sake of health, such as viruses. "
The researchers now use their experimental system to study the properties of mucus and the effects of therapies in other airway diseases.
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