Document Detail

Effect of stretch on structural integrity and micromechanics of human alveolar epithelial cell monolayers exposed to thrombin.
MedLine Citation:
PMID:  16399786     Owner:  NLM     Status:  MEDLINE    
Alveolar epithelial cells in patients with acute lung injury subjected to mechanical ventilation are exposed to increased procoagulant activity and mechanical strain. Thrombin induces epithelial cell stiffening, contraction, and cytoskeletal remodeling, potentially compromising the balance of forces at the alveolar epithelium during cell stretching. This balance can be further compromised by the loss of integrity of cell-cell junctions in the injured epithelium. The aim of this work was to study the effect of stretch on the structural integrity and micromechanics of human alveolar epithelial cell monolayers exposed to thrombin. Confluent and subconfluent cells (A549) were cultured on collagen-coated elastic substrates. After exposure to thrombin (0.5 U/ml), a stepwise cell stretch (20%) was applied with a vacuum-driven system mounted on an inverted microscope. The structural integrity of the cell monolayers was assessed by comparing intercellular and intracellular strains within the monolayer. Strain was measured by tracking beads tightly bound to the cell surface. Simultaneously, cell viscoelasticity was measured using optical magnetic twisting cytometry. In confluent cells, thrombin did not induce significant changes in transmission of strain from the substrate to overlying cells. By contrast, thrombin dramatically impaired the ability of subconfluent cells to follow imposed substrate deformation. Upon substrate unstretching, thrombin-treated subconfluent cells exhibited compressive strain (9%). Stretch increased stiffness (56-62%) and decreased cell hysteresivity (13-22%) of vehicle cells. By contrast, stretch did not increase stiffness of thrombin-treated cells, suggesting disruption of cytoskeletal structures. Our findings suggest that thrombin could exacerbate epithelial barrier dysfunction in injured lungs subjected to mechanical ventilation.
Xavier Trepat; Ferranda Puig; Nuria Gavara; Jeffrey J Fredberg; Ramon Farre; Daniel Navajas
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-01-06
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  290     ISSN:  1040-0605     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-05-10     Completed Date:  2006-08-11     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  L1104-10     Citation Subset:  IM    
Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Casanova 143, 08036 Barcelona, Spain.
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MeSH Terms
Cell Line
Cells, Cultured
Pulmonary Alveoli / cytology,  drug effects,  physiology*
Respiratory Mucosa / cytology,  drug effects,  physiology*
Stress, Mechanical
Thrombin / pharmacology*
Grant Support
Reg. No./Substance:

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