An investigation of the role of mucin gels in disease progression and transmission

Mucus is a biological hydrogel that coats every wet epithelial surface of the body, including the respiratory tract. Within the body, mucus serves as a barrier: a mesh network made of mucin polymers that act as a size and biochemical filter, trapping small molecules, including pathogens. When mucus is cleared from the respiratory tract via exhalations such as coughing or sneezing, it can act as a vessel for infectious material from infected individuals that can be carried to other potential hosts or remain in the environment. The high shear rates associated with violent exhalations cause respiratory mucus to fragment into droplets spanning a range of sizes. Once emitted, droplets are propelled to nearby surfaces or entrained and advected in ambient air flows. Larger droplets may settle quickly to the ground, whereas smaller aerosolized droplets may remain suspended in the air and evaporate over time. In this thesis, we investigate the role of mucins in these within-host and external disease processes. In mucosal layers within the host, mucus plays an important role in limiting the progression of infectious pathogens. The pathogen’s ability to penetrate mucus, in many cases, determines its ability to reach its target cell and initiate infection before being cleared by the body. We begin by studying the impact of mucins on the transport of virus-sized particles. First, we examine the transport of bacteriophage, a model system for viruses, and nanoparticles of comparable size in reconstituted mucin gels simulating the respiratory tract and intestinal environment. Our findings reveal that phage have different transport abilities tied to their geometry, size, and surface chemistry. In addition, they are relatively unhindered in concentrated mucin gels compared to similar-sized nanoparticles. We show that in different phage populations, diffusive Brownian motion is associated with both Gaussian (normally distributed) and non-Gaussian population-level and particle-level step size distributions, which consequently ...