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Am J Physiol Lung Cell Mol Physiol 275: L1173-L1183, 1998;
1040-0605/98 $5.00
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Vol. 275, Issue 6, L1173-L1183, December 1998

Equibiaxial deformation-induced injury of alveolar epithelial cells in vitro

Daniel J. Tschumperlin and Susan S. Margulies

Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104

Deformation of the alveolar epithelial basement membrane with lung inflation has been implicated in blood-gas barrier breakdown during the development of ventilator-induced lung injury. To determine the vulnerability of alveolar epithelial cells to deformation-induced injury, we developed a cell-stretching device that subjects cells to cyclic, equibiaxial strains. Alveolar epithelial type II cells from primary culture were tested 1 and 5 days after seeding, during which time the cells underwent major morphological and phenotypic changes. Cells were subjected to changes in surface area of 12, 24, 37, and 50%, which corresponded to lung inflation of ~60, 80, 100, and >100% of total lung capacity. Deformation-induced injury of alveolar epithelial cells, assessed with a fluorescent cell viability assay, increased with deformation magnitude and decreased with time elapsed after seeding. In cells stretched after 1 day in culture, the percentage of dead cells after a single deformation ranged from 0.5 to 72% over the range of deformations used. In cells stretched at 5 days, the percentage of dead cells ranged from 0 to 9% when exposed to identical deformation protocols. These results suggest that morphological and phenotypic changes with time in culture fundamentally change the vulnerability of alveolar epithelial cells to deformation.

cell mechanics; pulmonary mechanics; barotrauma; lung injury


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