Modelling the Squishy Effect in Interstitial Pulmonary Fibrosis

In idiopathic pulmonary fibrosis (IPF), the juxtaposition of preserved regions and fibrotic areas creates heterogeneous lung mechanics and abnormal stress environments, which are hypothesized to activate mechanotransduction pathways and drive fibrosis progression. This study uses the “squishy ball lung” concept to quantify the potentially injurious mechanical stimuli arising from this heterogeneity. We developed a mechanical model that simulates the static inflation of an alveolus. This is described as a hyperelastic membrane with surface tension that is partially confined by springs representing fibrotic tissue. Finite element analysis (FEA) was used to assess the mechanical state under various confinement conditions. FEA revealed bulging deformation and significant meridian stress/strain peaks at transitions between confined and unconfined zones, which could potentially exceed safe physiological limits. To rigorously evaluate the predicted stress and strain environment, as well as its sensitivity to parameter uncertainty, such as material properties and the extent of confinement, we performed comprehensive uncertainty quantification (UQ) and quantitative sensitivity analysis (QSA). UQ confirmed the robustness of these localized stress peaks across parameter variations, while QSA identified the angle of confinement and spring stiffness as the primary determinants of peak stress magnitude. By quantifying these potentially injurious stress peaks, this study provides insights into the mechanical environment hypothesized to initiate mechanotransduction pathways in idiopathic pulmonary fibrosis (IPF), laying the groundwork for future studies that incorporate biological responses such as growth and remodeling.