In response to respiratory insults, airway submucosal glands secrete copious mucus strands to increase mucociliary clearance and protect the lung. However, in cystic fibrosis, stimulating submucosal glands has the opposite effect, disrupting mucociliary transport. In cystic fibrosis (CF) pigs, loss of cystic fibrosis transmembrane conductance regulator (CFTR) anion channels produced submucosal gland mucus that was abnormally acidic with an increased protein concentration. To test whether these variables alter mucus, we produced a microfluidic model of submucosal glands using mucus vesicles from banana slugs. Acidic pH and increased protein concentration decreased mucus gel volume and increased mucus strand elasticity and tensile strength. However, once mucus strands were formed, changing pH or protein concentration largely failed to alter the biophysical properties. Likewise, raising pH or apical perfusion did not improve clearance of mucus strands from CF airways. These findings reveal mechanisms responsible for impaired mucociliary transport in CF and have important implications for potential treatments.

为应对呼吸道损伤，气道黏膜下腺体会分泌大量黏液，以增加黏液纤毛清除率并保护肺部。然而，在囊性纤维化中，刺激黏膜下腺体会产生相反的效果，破坏黏膜纤毛运输。在囊性纤维化 (CF) 猪中，囊性纤维化跨膜电导调节剂 (CFTR) 阴离子通道的丧失会产生异常酸性的黏膜下腺粘液，并且蛋白质浓度增加。为了测试这些变量是否会改变粘液，我们使用来自香蕉蛞蝓的粘液囊泡制作了粘膜下腺体的微流体模型。酸性 pH 值和增加的蛋白质浓度降低了粘液凝胶体积并增加了粘液链弹性和拉伸强度。然而，一旦形成粘液链，改变 pH 值或蛋白质浓度在很大程度上未能改变生物物理特性。同样，提高 pH 值或根尖灌注不会改善粘液从 CF 气道中的清除。这些发现揭示了导致 CF 中黏液纤毛运输受损的机制，并对潜在治疗具有重要意义。