Mucus hydrates and lubricates the eyes, the nose, the lungs, and the digestive and urogenital tracts. It gets its slippery, wet qualities from mucins — biopolymers with a protein backbone encrusted with sugars. If mucins are scarce or compromised, health problems result, including dry eye, dry mouth, an increased susceptibility to microbial infections, and a compromised ability to absorb food.
But, just as there is no substitute for human blood, there are no good substitutes yet for mucin. MIT researchers are exploring how mucin works in hopes of eventually developing substitutes.
Thomas Crouzier, a postdoctoral fellow at MIT's Laboratory for Biological Hydrogels, recently demonstrated, through research on mucus from pig stomachs, that the sugars in mucin play a key role in its ability to absorb water and provide lubrication. And he discovered a way to restore these qualities to mucins stripped of their sugars. Working with Johnson & Johnson scientists and MIT colleagues, Crouzier showed that substituting polyethylene glycol chains for missing sugar molecules can partly restore mucin's water-absorbing capacity and lubricating potential.
This work is a starting point toward recovering loss of function in altered mucins, and designing fully synthetic mucins. Besides Crouzier, MIT professor Katharina Ribbeck, graduate student Nicole Kavanaugh, and Johnson & Johnson scientists Anthony R. Geonnotti and Julie B. Hirsch are co-authors of a manuscript that is in preparation.
The ability of mucin polymers to hold large amounts of water is critical to keeping our epithelial cells healthy. Understanding how mucins do this could lead to better treatments for when they fail.
As part of the research, Crouzier measured the amount of water that mucins could bind. "The mucins on the surface [of mucus] will absorb a lot of water,” Crouzier says. “The coating that is formed on the surface is 90 percent water. Other proteins that I've tested here bind a lot less water.”
In friction tests, graduate student Nicole Kavanaugh and Johnson & Johnson scientists Anthony R. Geonnotti and Julie B. Hirsch found that a solution containing mucins is several orders of magnitude slipperier than a solution that just contains salts. "It shows you how very efficient this molecule is at lubricating surfaces," Crouzier says.
Crouzier studied the role of mucin-attached glycans (sugars) in water absorbency and lubrication because they make up from half to almost 90 percent of mucins’ weight and are known to be highly water-absorbent. Crouzier's experiments showed that stripping the mucins of some or all of their attached sugars robs them of both their sponge-like absorbency and their lubricating ability. "That tells us that the sugars are really important for both of these properties," he says.
The sugars, which give mucins a brush-like extended structure, may also aid lubrication by keeping the protein backbone from rolling into a ball. "When you remove the sugars, they can fold and be more globular and collapsed, so there is less space to hold water on the surface,” Crouzier says.
Some synthetic polymers such as polyethylene glycol (PEG) share mucins’ ability to hydrate and lubricate surfaces. Crouzier found that grafting polyethylene glycol to mucins stripped of sugars could recover some of their lost lubricative and wetting properties. A sugar-binding lectin (wheat germ agglutinin, or WGA) was used to link the polyethylene glycol to the mucins.
Although Crouzier's demonstration that polyethylene glycol could bind to mucin in place of sugars presents a clear biological-engineering solution to a common problem, much more work will be necessary before it can be implemented in commercial products. Lectins such as WGA can be toxic to certain types of cells. However, in preliminary studies Crouzier conducted with bacteria, immune cells, and zebrafish embryos, "we saw that lectins alone at high concentration can be toxic, but once attached to the polyethylene glycol, they lose their toxicity," Crouzier says.