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This Article Full Text Full Text (PDF) All Versions of this Article: 292/1/L40    most recent 00425.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Fisher, J. L. Articles by Margulies, S. S. Search for Related Content PubMed PubMed Citation Articles by Fisher, J. L. Articles by Margulies, S. S.

Modeling the effect of stretch and plasma membrane tension on Na⁺-K⁺-ATPase activity in alveolar epithelial cells

¹Department of Bioengineering, and ²Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania

Submitted 4 October 2005 ; accepted in final form 24 July 2006

While a number of whole cell mechanical models have been proposed, few, if any, have focused on the relationship among plasma membrane tension, plasma membrane unfolding, and plasma membrane expansion and relaxation via lipid insertion. The goal of this communication is to develop such a model to better understand how plasma membrane tension, which we propose stimulates Na⁺-K⁺-ATPase activity but possibly also causes cell injury, may be generated in alveolar epithelial cells during mechanical ventilation. Assuming basic relationships between plasma membrane unfolding and tension and lipid insertion as the result of tension, we have captured plasma membrane mechanical responses observed in alveolar epithelial cells: fast deformation during fast cyclic stretch, slower, time-dependent deformation via lipid insertion during tonic stretch, and cell recovery after release from stretch. The model estimates plasma membrane tension and predicts Na⁺-K⁺-ATPase activation for a specified cell deformation time course. Model parameters were fit to plasma membrane tension, whole cell capacitance, and plasma membrane area data collected from the literature for osmotically swollen and shrunken cells. Predictions of membrane tension and stretch-stimulated Na⁺-K⁺-ATPase activity were validated with measurements from previous studies. As a proof of concept, we demonstrate experimentally that tonic stretch and consequent plasma membrane recruitment can be exploited to condition cells against subsequent cyclic stretch and hence mitigate stretch-induced responses, including stretch-induced cell death and stretch-induced modulation of Na⁺-K⁺-ATPase activity. Finally, the model was exercised to evaluate plasma membrane tension and potential Na⁺-K⁺-ATPase stimulation for an assortment of traditional and novel ventilation techniques.

ventilator-induced lung injury; lipid trafficking; edema recovery