title: Role of deformation-induced lipid trafficking in the prevention of plasma membrane stress failure.
abstract: Cells experience plasma membrane stress failure when the matrix to which they adhere undergoes large deformations. In the lung, such a mechanism might explain mechanical ventilation-associated cell injury. We have previously shown that in alveolar epithelial cells, deformation induces lipid trafficking to the plasma membrane, thereby accommodating the required increase in the cell surface area. We now show that cell wounding is strain amplitude and rate dependent and that under conditions of impaired exocytosis strain-induced cell wounding is significantly increased. In addition, the susceptibility of cells to mechanical injury was not correlated with changes in cell stiffness. Using a dual-labeling technique, we differentiated between cell populations that were reversibly and irreversibly injured and showed that interventions that impair deformation-induced lipid trafficking also reduce the likelihood of plasma membrane resealing. Our findings suggest that cell plasticity and remodeling responses such as deformation-induced lipid trafficking are more important for cytoprotection from strain injury than are the innate mechanical properties of the cell. We also conclude that in deformation experiments, tests of cell membrane integrity cannot be interpreted as tests of cell viability because an intact plasma membrane after deformation does not mean that no injury had occurred.
authors.affiliation: Pulmonary and Critical Care Medicine Division, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA. vlahakis.nicholas@mayo.edu
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Vlahakis
authors.forename: Mark A
authors.initials: MA
authors.lastname: Schroeder
authors.forename: Richard E
authors.initials: RE
authors.lastname: Pagano
authors.forename: Rolf D
authors.initials: RD
authors.lastname: Hubmayr
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000502:physiology* / Q000648:ultrastructure*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000502:physiology / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D066298:In Vitro Techniques; D008563:Membrane Lipids / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000503:physiopathology / Q000648:ultrastructure; D051381:Rats; D013312:Stress, Physiological / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D008563:Membrane Lipids