title: Image-based finite element modeling of alveolar epithelial cell injury during airway reopening.
abstract: The acute respiratory distress syndrome (ARDS) is characterized by fluid accumulation in small pulmonary airways. The reopening of these fluid-filled airways involves the propagation of an air-liquid interface that exerts injurious hydrodynamic stresses on the epithelial cells (EpC) lining the airway walls. Previous experimental studies have demonstrated that these hydrodynamic stresses may cause rupture of the plasma membrane (i.e., cell necrosis) and have postulated that cell morphology plays a role in cell death. However, direct experimental measurement of stress and strain within the cell is intractable, and limited data are available on the mechanical response (i.e., deformation) of the epithelium during airway reopening. The goal of this study is to use image-based finite element models of cell deformation during airway reopening to investigate how cell morphology and mechanics influence the risk of cell injury/necrosis. Confocal microscopy images of EpC in subconfluent and confluent monolayers were used to generate morphologically accurate three-dimensional finite element models. Hydrodynamic stresses on the cells were calculated from boundary element solutions of bubble propagation in a fluid-filled parallel-plate flow channel. Results indicate that for equivalent cell mechanical properties and hydrodynamic load conditions, subconfluent cells develop higher membrane strains than confluent cells. Strain magnitudes were also found to decrease with increasing stiffness of the cell and membrane/cortex region but were most sensitive to changes in the cell's interior stiffness. These models may be useful in identifying pharmacological treatments that mitigate cell injury during airway reopening by altering specific biomechanical properties of the EpC.
authors.affiliation: Dept. of Biomedical Engineering, Lehigh University, Bethlehem, Pennsylvania, USA.
authors.forename: H L
authors.initials: HL
authors.lastname: Dailey
authors.forename: L M
authors.initials: LM
authors.lastname: Ricles
authors.forename: H C
authors.initials: HC
authors.lastname: Yalcin
authors.forename: S N
authors.initials: SN
authors.lastname: Ghadiali
mesh_terms: D001696:Biomechanical Phenomena; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000473:pathology; D048430:Cell Shape; D004548:Elasticity; D004847:Epithelial Cells / Q000473:pathology*; D020342:Finite Element Analysis; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D008560:Membrane Fluidity; D018613:Microscopy, Confocal; D008954:Models, Biological; D009336:Necrosis; D011650:Pulmonary Alveoli / Q000293:injuries / Q000473:pathology*; D013314:Stress, Mechanical; D055397:Ventilator-Induced Lung Injury / Q000473:pathology*; D014783:Viscosity