HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Am J Physiol Lung Cell Mol Physiol 295: L849-L857, 2008. First published August 15, 2008; doi:10.1152/ajplung.00503.2007
1040-0605/08 $8.00

This Article Free upon publication Full Text Full Text (PDF) All Versions of this Article: 295/5/L849    most recent 00503.2007v1 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 PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Felder, E. Articles by Dietl, P. PubMed PubMed Citation Articles by Felder, E. Articles by Dietl, P.

Mechanical strain of alveolar type II cells in culture: changes in the transcellular cytokeratin network and adaptations

¹Institute for General Physiology, University of Ulm, Ulm; ²Department of Internal Medicine I, University Hospital Ulm, Ulm; and ³Central Facility for Electron Microscopy, University of Ulm, Ulm, Germany

Submitted 7 December 2007 ; accepted in final form 14 August 2008

Mechanical forces exert multiple effects in cells, ranging from altered protein expression patterns to cell damage and death. Despite undisputable biological importance, little is known about structural changes in cells subjected to strain ex vivo. Here, we undertake the first transmission electron microscopy investigation combined with fluorescence imaging on pulmonary alveolar type II cells that are subjected to equibiaxial strain. When cells are investigated immediately after stretch, we demonstrate that curved cytokeratin (CK) fibers are straightened out at 10% increase in cell surface area (CSA) and that this is accompanied by a widened extracellular gap of desmosomes–the insertion points of CK fibers. Surprisingly, a CSA increase by 20% led to higher fiber curvatures of CK fibers and a concurrent return of the desmosomal gap to normal values. Since 20% CSA increase also induced a significant phosphorylation of CK8-ser431, we suggest CK phosphorylation might lower the tensile force of the transcellular CK network, which could explain the morphological observations. Stretch durations of 5 min caused membrane injury in up to 24% of the cells stretched by 30%, but the CK network remained surprisingly intact even in dead cells. We conclude that CK and desmosomes constitute a strong transcellular scaffold that survives cell death and hypothesize that phosphorylation of CK fibers is a mechano-induced adaptive mechanism to maintain epithelial overall integrity.

mechanical stress; cytoskeleton; desmosome; injury