Of all the things that you could study, few would ever think (never mind dream) of researching mucus. Yet for Professor Katharina Ribbeck, these “biological hydrogels” that take on different forms throughout the body are fascinating. “I was captivated by just how important mucus barriers are, as well as how understudied they seem to be.” Most people have heard of the genetic disorder cystic fibrosis that causes thick bronchial mucus to clog the lungs and makes it difficult for people with the condition to breathe. But what impact does mucus have in other parts of the human body?

Contrary to how it may seem, mucus is not just some unsavory waste product – it actually helps our bodies to function, especially when ensuring that our epithelial tissues remain moist. “Mucus is an excellent lubricant that enables us to do things as simple as close our eyes and swallow. Olfactory cells in the nose and taste buds on the tongue are also embedded within mucus membranes.” A considerable part of the human microbiome – especially our gut microbiota – is sustained by mucus. “To date, no synthetic material has been able to support and nourish such a diverse microbial community.”

Breaking Down Mucus to Better Understand It

The German biologist breaks down mucus into its most basic components at Massachusetts Institute of Technology (MIT) in Cambridge, MA, in order to understand which of them are essential for its different functions. Mucus is mostly made up of molecules called mucins. These networks of polymers consisting of hygroscopic glycoproteins look like bottle brushes, with the “bristles” attached to the amino acids made from shorter sugar chains. Professor Rainer Haag, a polymer chemist at Freie Universität Berlin, has been investigating how to synthetically produce these thread-like structures to resemble natural mucus. One day it may even be possible to use synthetic mucus to treat patients. Both working groups are currently collaborating and learning from each other as part of the German Research Foundation’s Mercator program.

Professor Ribbeck started on her journey to becoming a mucus expert at Heidelberg University, where she studied biology and later earned her doctorate on the topic of how substances are transported through the nuclear membrane. “The nuclear membrane has lots of tiny pores that are filled with a slimy substance. This gel, which is a close relation of mucus, is a polymer network with thread-like structures. Some particles are able to move through it, while others are not. And I thought to myself that this can’t be the only example of something like that in the whole sphere of biology,” says Ribbeck.

Later in her career, a colleague at Harvard Medical School in Boston invited her to conduct research with him for a year. Soon she came across an opportunity to set up her own junior research group at Harvard University for five years. The only condition was that they would need to work on a totally unexplored field of research. Ribbeck laughs, “That was the big draw for me! I thought to myself, ‘Well, I suppose it’s time to bring mucus into the equation.’”

She started off analyzing saliva, the mucus that’s most easily accessible in humans. Soon she began studying mucus from pig’s gastrointestinal tracts, which is relatively easy to isolate in large quantities. Then she moved on to researching human cervical mucus, which is secreted by glands found in the cervix, to study the connection between certain types of infertility and mucosal barrier issues.

How Do Pharmaceutical Drugs Reach Their Target?

Initially Ribbeck was interested in the principles of simple selectivity, like which properties allow a particle to pass through mucus, and which particles remain suspended in the substance. This is important for understanding how pharmaceutical drugs reach their target within the body. For example, whether a substance is inhaled or swallowed, it will always have to pass through a mucus layer.

It turns out that mucus isn’t a sticky filter that just catches stray pathogens. Ribbeck conducted experiments by embedding bacteria in mucus and found that they managed to struggle their way through the substance. “The polymers of intact mucus are very good at preventing microbes from forming large colonies without killing them off. They are instead mixed in with other species, and this makes it more difficult for these pathogens to cause infections.” This results in greater biodiversity in the microbiome. “Even corals have a layer of mucus. The types of bacteria recruited by the organism in order to capture, consume, and excrete nutrients depend on its characteristics and quality.” As such, mucus is a very special, highly active biological gel that allows living creatures to interact with the outside world and absorb certain types of “information,” while keeping other information at bay.

Mucins are produced by cells in the mucous membrane. They fill small capsules called vesicles and are secreted when needed. “This is a unique process, as glycoproteins are stored in a dry state and expand their original size hundreds of times when hydrated.” This is similar to when pasta swells up as it cooks – except that in this case, three or four noodles would end up filling the entire pot. The mucins intermingle and become part of a network as they grow.

Two Hundred Square Meters of Mucus

If you were to calculate the surface area covered by mucus in the adult human body, it would come to about two hundred square meters. “Mucus production is a massive undertaking for the body,” Ribbeck says. Depending on where it is secreted, mucus plays a variety of different roles that are reflected in its composition and viscosity. There are actually only about twenty different types of mucins in the body. They differ in length and in the make-up of their sugar chains, with the latter being specific to particular surfaces. “And then there are biophysical differences that arise depending on the type of networks and pH value where the mucin is in operation,” says Ribbeck. That means that the exact same mucin that can be found in the lungs – which have an almost completely neutral pH value – is very thin, while in the acidic environment of the stomach it is condensed into an almost rubber-like substance to protect the wall of the stomach from digesting itself. When the properties of a material transform due to external influences, researchers refer to this type of substance as a “smart material.”

Ribbeck is unsure if she will take up permanent residency in the US. “I really like it at MIT. But I’m a European at heart – and always will be.” However, the forty-seven-year-old already has an idea of where she’d like to branch off to next in her research. She can’t stop thinking about the gut-brain axis, a concept revolving around the idea that microbes that live on and within our bodies can influence our mental state: “The microbiome changes during bouts of stress and depressive episodes, and mucus plays a significant role here.”

She has also been reflecting on whether healthy microbes could offer better anchor points in mucus, so that bacteria with new properties could be implanted there to extract specific substances from food that the body itself cannot produce. Ribbeck says that it all depends on the mucus getting the right nutrition: “In this way, mucus resembles soil: If it doesn’t get the right nutrients, then you won’t be able to grow certain things.” Studying mucus can be slippery business, but it’s a research field with a lot of potential.

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This article originally appeared in German on September 27, 2022, in the Tagesspiegel newspaper supplement published by Freie Universität Berlin.