Abstract
This study presents a full three-dimensional multiscale computational model of lung parenchyma to investigate how heterogeneous alveolar ventilation generates regions of high stress. The model integrates elastin and collagen fiber mechanics at the alveolar level to capture microstructural interactions. Simulations of nonuniform alveolar pressure, particularly in the presence of atelectasis (collapsed lung regions), reveal significant localized distortions in adjacent normal parenchyma, especially along the atelectatic boundary. Results demonstrate that heterogeneous ventilation induces substantial stress concentrations in surrounding healthy tissue, which may contribute to lung injury and disease progression in acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury (VILI). A reduced-dimension periacinar pressure model is introduced to provide a simplified yet effective framework for analyzing these mechanical interactions. Notably, the model shows that even under seemingly normal transmural pressures, alveolar collagen fibers near atelectatic regions experience extreme tensile stresses, which could be misinterpreted as microvolutrauma despite originating from atelectasis. These findings underscore the critical role of heterogeneous ventilation in driving injurious mechanical forces within the lung, highlighting the need for ventilation strategies that minimize airway closure or alveolar derecruitment.