PT - JOURNAL ARTICLE AU - Daniel Song AU - Ethan Iverson AU - Logan Kaler AU - Margaret A. Scull AU - Gregg A. Duncan TI - MUC5B mobilizes and MUC5AC spatially aligns mucociliary transport on human airway epithelium AID - 10.1101/2022.03.11.484020 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.03.11.484020 4099 - http://biorxiv.org/content/early/2022/03/13/2022.03.11.484020.short 4100 - http://biorxiv.org/content/early/2022/03/13/2022.03.11.484020.full AB - 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.Competing Interest StatementThe authors have declared no competing interest.