Electrostatic Interactions Control the Permeability of Mucin Hydrogels

Abstract

Biological functional entities surround themselves with selective barriers which control the passage of certain classes of macromolecules while rejecting others. A prominent example of such a selective permeability barrier is given by mucus. Mucus is a biopolymer based hydrogel which lines all wet epithelial surfaces of the human body. It regulates the uptake of nutrients from our gastrointestinal system, adjusts itself with the menstrual cycle to control the passage of sperm, and shields the underlying cells from pathogens such as bacteria and viruses. In the case of drug delivery, the mucus barrier needs to be overcome for successful medical treatment. Despite its importance for both physiology and medical applications, the underlying principles which regulate the permeability of mucus remain enigmatic. Here, we analyze the mobility of microscopic particles in reconstituted mucus hydrogels. We show that electrostatic interactions between diffusing particles and mucin polymers set the permeability of reconstituted mucin hydrogels. As a consequence, various parameters such as particle surface charge, mucin density and buffer conditions such as pH and ionic strength can sensitively modulate the microscopic barrier function of the mucin hydrogel. Our findings demonstrate the wide range of permeability that operates in different compartments of our bodies, employing the very same biopolymer based hydrogel.