MUC5B mobilizes and MUC5AC spatially aligns mucociliary transport on human airway epithelium

Abstract Airway mucus acts as a protective barrier and vehicle for clearance of pathogens, providing the lungs with a defense mechanism called mucociliary clearance (MCC). Airway mucus is composed of two mucins, mucin 5B (MUC5B) and 5AC (MUC5AC) that form a hydrogel that enables functional clearance in health. However, abnormalities in mucin expression, specifically increases in MUC5AC is observed in chronic respiratory diseases and leading to defective MCC. Our current understanding of MCC impairment focuses on mucin concentration, while the impact of mucin composition remains unclear. Here, we use MUC5AC/B-knock out (KO) human airway epithelial (HAE) tissue cultures to understand the role and contribution of individual secreted mucins on MCC mechanisms. We find that KO cultures result in impaired or discoordinated mucociliary transport demonstrating the importance of each of these mucins to effective MCC and shedding light on a new mechanism of mucin composition-dependent airway clearance.