Frequency and Peak Stretch Magnitude Affect Alveolar Epithelial Permeability

¹ Dept of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104-6321

^* To whom correspondence should be addressed. E-mail: margulie{at}seas.upenn.edu.

	Abstract

We measured stretch-induced changes in transepithelial permeability to uncharged tracers (1.5–5.5 Å) using cultured monolayers of alveolar epithelial type I "like" cells. Cultured alveolar epithelial cells were subjected to uniform cyclic (0, 0.25, and 1.0 Hz) biaxial stretch from 0% to 12%, 25%, or 37% change in surface area (SA) for 1 hour. Significant changes in permeability of cell monolayers were observed when stretched from 0% to 37% SA at all frequencies, when stretched from 0% to 25% SA only at high frequency (1 Hz), and not at all when stretched from 0 to 12% SA compared to unstretched controls. Cells subjected to a single stretch cycle at 37% SA (0.25 Hz), to simulate a deep sigh, were not distinguishable from unstretched controls. Reducing stretch oscillation amplitude while maintaining peak stretch of 37% SA (0.25 Hz) via the application of a simulated post end expiratory pressure, or PEEP, did not protect barrier properties. At stretch oscillation amplitudes of 25 and 37% SA, imposed at 1 Hz, tracer permeability increased compared to 0.25 Hz. We concluded that peak stretch magnitude and stretch frequency were the primary determining factors for epithelial barrier dysfunction, as opposed to oscillation amplitude.