The role of fluid dynamics, microstructure and mucociliary clearance in the micro- and macroscopic barrier properties of pulmonary mucus

摘要

Major issues in both toxicological as well as pharmaceutical research are biological barriers, impeding the invasion of pathogens but also the delivery of beneficial substances into the body. The upper lungs as site of application of such substances exhibit a particularly efficient biological barrier: the mucus blanket and its mucociliary clearance. The fate of particles upon deposition onto the moving mucus barrier is yet unsolved and was central theme of this work. In this context, mucociliary clearance of nanoparticles and its fluid dynamics were investigated. These results were correlated with the analysis of microscopic and macroscopic particle penetration behavior in mucus and mucus structure. Here, the application of complex methods such as cryoscopic scanning electron microscopy (cryo-SEM), atomic force microscopy (AFM) and optical tweezers revealed the mechanisms of particle mobility in mucus. It could be shown that mucociliary clearance is independent on particle properties such as size, shape, charge or surface chemistry. It was demonstrated that this is due to the only poor particle mobility in mucus: The polymer scaffold of mucus is highly rigid which, in combination with the extensive heterogeneity in pore size, impedes particle translocation. In contrast to model gels and due to this rigidity, particles in mucus which are exposed to external force fields cannot deform or rupture the polymer scaffold of mucus.