Physical properties of mucus barriers
Mucus is an ideal system in which to elucidate general principles of hydrogel filtration properties. It can be obtained in bulk both in native form and from cell lines that secrete mucus, and can also be reconstituted from its basic constituent, the mucin glycoprotein. We study the mobility within mucus of macromolecules of different sizes, polar and non-polar proteins, nucleic acids, and viruses. We use single particle tracking and bulk measurements to measure mobility as a function of time and distance, and determine whether movement occurs by normal (Fickian) diffusion or anomalous (non-Fickian) diffusion. Anomalous diffusion has been noted in various biological systems, but its mechanistic basis and biological function have been difficult to analyze. In the case of mucus, where we can make accurate measurements of particle movement, and systematically alter the properties of both the gel and the moving particles, we should be able to relate physical properties to biological function in a quantitative manner.

To understand hydrogels we also need to understand how the structure of individual polymers

and the interactions between them allows them to generate selective filters.

Most biological gels include many sugar residues; mucus contains long-chain N- and O-glycans, while nuclear pore components are monoglycosylated with O-linked N-acetylglucosamin. The biological function of sugars (outside metabolism) is little understood; controlling the filtration properties of hydrogels may be one of their central functions. Indeed, alterations in mucin glycosylation correlate with changes in tissue film properties and are typical for ovulation, and are also associated with the pathogenesis of cancer and other diseases. We investigate the effect of altering the extent of mucin glycosylation on the permeability and viscoelasticity of mucin gels.

Fig: What makes a hydrogel selective? What is the meshsize of the gel? Does the gel polymer engage in interactions with particles? How do internal hydrogel interactions look like, and what is the dynamics of the whole system?