Biophysical mechanisms of mucostasis in the airways and their modeling: the role of osmotic balance and the «gel on brush» model

Objective. To systematize current concepts of the airway mucus barrier structure and biophysical mechanisms of mucociliary transport, including the «gel on brush» concept, and to analyze their role in the pathogenesis of mucostasis. Material and methods. A search and analysis of publications in PubMed/MEDLINE, Web of Science, eLIBRARY.RU (2010—2026) was performed. Original studies and reviews on mucin structure, physiology of the periciliary layer, the «gel on brush» model, pathophysiology of cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD) and bronchial asthma were included. The final bibliography contains 24 sources. Results. Mucociliary clearance consists of a mucus layer and the periciliary layer (PCL). The «gel on brush» model (Button B. et al., 2012) posits that the PCL contains a dense network of membrane-tethered mucins (MUC1, MUC4, MUC16, MUC20) forming an extracellular “brush” with a mesh size of 20—40 nm. This structure prevents penetration of polymeric MUC5AC/MUC5B mucins and creates an osmotic barrier. Normally, the osmotic pressure of mucus (~200 Pa) is lower than the PCL modulus (~300 Pa). During dehydration (CF) or mucin hypersecretion (COPD) it exceeds the threshold, causing collapse of the brush layer and arrest of mucociliary transport. Conclusion. The «gel on brush» model is experimentally substantiated and quantitatively explains the pathogenesis of mucostasis in CF, COPD, and asthma. Its implementation opens prospects for targeted correction of mucus rheological properties. Development of methods for in vivo visualization of the brush layer is required for early diagnosis of airway dehydration.