Modeling the influence of gravity and the mechanical properties of elastin and collagen fibers on alveolar and lung pressure–volume curves

The relationship between pressure (P) and volume (V) in the human lung has been extensively studied. However, the combined effects of gravity and the mechanical properties of elastin and collagen on alveolar and lung P–V curves during breathing are not well understood. Here, we extended a previously established thick-walled spherical model of a single alveolus with wavy collagen fibers during positive pressure inflation. First, we updated the model for negative pressure-driven inflation that allowed incorporation of a gravity-induced pleural pressure gradient to predict how the static alveolar P–V relations vary spatially throughout an upright human lung. Second, by introducing dynamic surface tension and collagen viscoelasticity, we computed the hysteresis loop of the lung P–V curve. The model was tested by comparing its predicted regional ventilation to literature data, which offered insight into the effects of microgravity on ventilation. The model has also produced novel testable predictions for future experiments about the variation of mechanical stresses in the septal walls and the contribution of collagen and elastin fibers to the P–V curve and throughout the lung. The model may help us better understand how mechanical stresses arising from breathing and pleural pressure variations affect regional cellular mechanotransduction in the lung.