Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Dailey HL, Ricles LM, Yalcin HC, Ghadiali SN. Image-based finite element modeling of alveolar epithelial cell injury during airway reopening. J Appl Physiol 106: 221-232, 2009. First published November 13, 2008 doi:10.1152/japplphysiol.90688.2008.-The acute respiratory distress syndrome (ARDS) is characterized by fluid accumulation in small pulmonary airways. The reopening of these fluidfilled 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. flow-induced cell injury; epithelial cell mechanics; orthotropic membrane; ADINA CERTAIN PATHOLOGICAL CONDITIONS such as pneumonia and sepsis can lead to the development of the acute respiratory distress syndrome (ARDS), which is the most severe manifestation of acute lung injury (ALI). This condition is characterized by increased permeability of the alveolar-capillary barrier leading to fluid accumulation in the distal airways (43). In many cases, mechanical ventilation is necessary to stabilize patients with ARDS. However, ventilators can generate injurious mechanical forces that exacerbate the existing lung trauma. These mechanical forces, which are typically applied to lung epithelial cells (EpC), can cause cell necrosis (6, 46), further barrier disruption (9, 10, 46), and upregulation of inflammatory pathways (36). These mechanical and biological responses lead to additional lung injury known as ventilator-associated lung injury (VALI) (12). Although recent advances in ventilation protocols, including low tidal volu...

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Solvent-cast 3D printing with peptide–polymer conjugates introduces a versatile platform to spatially organize peptides to guide local cell behavior.