Coarse-grained Modeling and Experimental Investigation of the Viscoelasticity of Human Gut Mucus and Nanoparticle Dynamics

Abstract

A thick layer of mucus covering the gastrointestinal tract acts as an innate barrier guarding the epithelial surface. The high molecular weight and cross-linked glycoproteins (mucins), the major building blocks of mucus, can effectively obstruct or trap invading noxious substances, such as detrimental bacteria and virus. The mucus layer as well as any trapped material can be regularly removed by the friction force from food flow and gastrointestinal peristalsis, the process of which primarily relies on the viscoelastic and shear-thinning properties. Conversely, the process by which beneficial substances, such as drug nanoparticles, cross the mucus layer and contact the epithelium is also influenced by the chemical and rheological properties of the mucus layer. Gastrointestinal disorders, most notably colitis, are often accompanied by changes to the mucosal structure. In this study, we experimentally characterized the viscoelasticity and dynamic viscosity of mucus collected from human intestinal cells. In addition, we developed a bi-component mesoscopic-scale mucus model that contained Muc2, the dominant mucin secreted in healthy individuals, and Muc5AC, which is secreted by intestinal goblet cells in certain intestinal disorders. This model enabled us to study the effects of cross-linking and mucin concentration on rheological properties of mucus. Furthermore, we quantified changes in the diffusion dynamics of nanoparticles in mucus networks caused by factors such as the size of nanoparticles, nanoparticle-mucin interactions, and the degree of mucin cross-linking.