Equibiaxial deformation-induced injury of alveolar epithelial cells in vitro

Deformation of the alveolar epithelial basement membrane with lung inflatio n has been implicated in blood-gas barrier breakdown during the development of ventilator-induced lung injury. To determine the vulnerability of alveo lar epithelial cells to deformation-induced injury, we developed a cell-str etching device that subjects cells to cyclic, equibiaxial strains. Alveolar epithelial type II cells from primary culture were tested 1 and 5 days aft er seeding, during which time the cells underwent major morphological and p henotypic changes. Cells were subjected to changes in surface area of 12, 2 4, 37, and 50%, which corresponded to lung inflation of similar to 60, 80, 100, and >100% of total lung capacity. Deformation-induced injury of alveol ar epithelial cells, assessed with a fluorescent cell viability assay, incr eased with deformation magnitude and decreased with time elapsed after seed ing. In cells stretched after 1 day in culture, the percentage of dead cell s after a single deformation ranged from 0.5 to 72% over the range of defor mations used. In cells stretched at 5 days, the percentage of dead cells ra nged from 0 to 9% when exposed to identical deformation protocols. These re sults suggest that morphological and phenotypic changes with time in cultur e fundamentally change the vulnerability of alveolar epithelial cells to de formation.