Biological Significance of the Respiratory Mucus Rheology in Mucociliary Clearance

Abstract

Mucociliary clearance (MCC) is the first line of defense in the respiratory tract, where beating cilia and viscous mucus play a pivotal role in eliminating inhaled harmful substances. Homeostasis of mucus rheological properties is a crucial factor in maintaining the functionality of MCC. However, rheological properties of the mucus is poorly understood because of the challenges associated with collecting intact mucus samples. In this report, in vitro three-dimensionally cultured human bronchial epithelial cells were used as a source of mucus to investigate mucus rheological properties. The mucus exhibited rheopectic and shear-thinning behavior, and mucus viscosity increased over time under constant shear when the mucus concentration was high. In addition, intermittent interruption of shear forces caused further increases in mucus viscosity. The experimental conditions mimic disease-state-MCC (i.e., mucus hypersecretion and impaired ciliary function). Thus, the results match the high mucus viscosity found in respiratory disease patients. Inhibiting disulfide bonding and hydrophobic interactions between mucin molecules, which are authorized therapies for chest congestion, reduced the rheological behavior. The rheopectic behavior of respiratory mucus and its importance in MCC has been presented herein, and our experimental approach should facilitate drug discovery against respiratory diseases.