title: Influence of airway wall compliance on epithelial cell injury and adhesion during interfacial flows.
abstract: Interfacial flows during cyclic airway reopening are an important source of ventilator-induced lung injury. However, it is not known how changes in airway wall compliance influence cell injury during airway reopening. We used an in vitro model of airway reopening in a compliant microchannel to investigate how airway wall stiffness influences epithelial cell injury. Epithelial cells were grown on gel substrates with different rigidities, and cellular responses to substrate stiffness were evaluated in terms of metabolic activity, mechanics, morphology, and adhesion. Repeated microbubble propagations were used to simulate cyclic airway reopening, and cell injury and detachment were quantified via live/dead staining. Although cells cultured on softer gels exhibited a reduced elastic modulus, these cells experienced less plasma membrane rupture/necrosis. Cells on rigid gels exhibited a minor, but statistically significant, increase in the power law exponent and also exhibited a significantly larger height-to-length aspect ratio. Previous studies indicate that this change in morphology amplifies interfacial stresses and, therefore, correlates with the increased necrosis observed during airway reopening. Although cells cultured on stiff substrates exhibited more plasma membrane rupture, these cells experienced significantly less detachment and monolayer disruption during airway reopening. Western blotting and immunofluorescence indicate that this protection from detachment and monolayer disruption correlates with increased focal adhesion kinase and phosphorylated paxillin expression. Therefore, changes in cell morphology and focal adhesion structure may govern injury responses during compliant airway reopening. In addition, these results indicate that changes in airway compliance, as occurs during fibrosis or emphysema, may significantly influence cell injury during mechanical ventilation.
authors.affiliation: Biomedical Engineering Department, The Ohio State University, Columbus, Ohio;
authors.forename: Natalia
authors.initials: N
authors.lastname: Higuita-Castro
authors.affiliation: Biomedical Engineering Department, The Ohio State University, Columbus, Ohio;
authors.forename: Cosmin
authors.initials: C
authors.lastname: Mihai
authors.affiliation: Biomedical Engineering Department, The Ohio State University, Columbus, Ohio;
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Hansford
authors.affiliation: Biomedical Engineering Department, The Ohio State University, Columbus, Ohio; Department of Internal Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio; and Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio ghadiali.1@osu.edu.
authors.forename: Samir N
authors.identifier: http://orcid.org/0000-0002-6845-774X
authors.initials: SN
authors.lastname: Ghadiali
mesh_terms: D002448:Cell Adhesion; D002478:Cells, Cultured; D022001:Focal Adhesions / Q000502:physiology*; D006801:Humans; D008170:Lung Compliance; D020545:Respiratory Mucosa / Q000166:cytology / Q000293:injuries*; D055397:Ventilator-Induced Lung Injury / Q000209:etiology*
keywords: airway compliance; airway reopening; and cell injury; cell mechanics; ventilation-induced lung injury