Multiscale modeling of lung mechanics: From alveolar microstructure to pulmonary function

Abstract

The mechanical behavior of the lungs has long been associated with the structural properties of alveoli in pulmonary medicine. However, this structure-function relationship has mostly been qualitative, as experimentation in real lungs is costly and limited by ethical standards. Here we present a poromechanical multiscale model that connects key alveolar features with organ-level function. To this end, we first revisit an asymptotic homogenization framework for finite-deformation poromechanics and formulate fine-scale and coarse-scale problems that govern lung mechanics. We further inform the coarse-scale problem using a tetrakaidecahedron micromechanical model for the alveolar response at the fine scale that strongly depends on the alveolar-wall elastic modulus and the initial alveolar porosity. Based on this formulation, we construct a non-linear finite element model from anatomical geometries to simulate the response of human lungs connected to a mechanical ventilator under pressure-controlled and volume-controlled protocols. We show that the predicted signals for airway pressure, airway flow, and lung volume capture the dynamic waveform characteristics observed in human lungs. Further, we demonstrate that lung behavior, measured in terms of respiratory-system compliance, strongly depends on the alveolar-wall elasticity and alveolar porosity. In particular, we show that variations in these microstructural parameters result in marked changes in compliance that follow the structure-function relations observed in lungs with pulmonary fibrosis and emphysema, two prevalent chronic respiratory diseases. We envision that our multiscale lung model can enhance current in silico efforts to experimentation in respiratory research and provide a computational framework for clinically-relevant simulations. Codes are available for download at https://github.com/comp-medicine-uc/multiscale-lung-mechanics.