Understanding Bidirectional Water Transport across Bronchial Epithelial Cell Monolayers: A Microfluidic Approach

Abstract

Deciphering the dynamics of water transport across bronchial epithelial cell monolayers is pivotal for unraveling respiratory physiology and pathology. In this study, we employ an advanced microfluidic system to explore bidirectional water transport across 16HBE14σ bronchial epithelial cells. Previous experiments unveiled electroneutral multiple ion transport, with chloride ions utilizing transcellular pathways and sodium ions navigating both paracellular and transcellular routes. Unexpectedly, under isoosmotic conditions, rapid bidirectional movement of Na+ and Cl− was observed, leading to the hypothesis of a substantial transport of isoosmotic solution (145 mM NaCl) across cell monolayers. To validate this conjecture, we introduce an innovative microfluidic device, offering a 500-fold sensitivity improvement in quantifying fluid flow. This system enables the direct measurement of minuscule fluid volumes traversing cell monolayers with unprecedented precision. Our results challenge conventional models, indicating a self-regulating mechanism governing water transport that involves the CFTR channel and anion exchangers. In healthy subjects, equilibrium is achieved at an apical potential of Δφap = −30 mV, while subjects with cystic fibrosis exhibit modulation by an anion exchanger, reaching equilibrium at [Cl] = 67 mM in the airway surface liquid. This nuanced electrochemical basis for bidirectional water transport in bronchial epithelia sheds light on physiological intricacies and introduces a novel perspective for understanding respiratory conditions.