Lung architecture amplifies tissue deposition in an agent-based model of fibrotic development

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease where excessive extracellular matrix (ECM) deposition and remodeling stiffens the lung, impeding its function. Many factors are known to contribute to the development of this fibrosis, but a lack of conclusive understanding endures because of their complex nature. The modification of ECM and the unique architecture of the lung are such factors in IPFs propagation and not solely casualties. Their effects on fibrogenesis are not known and tricky to study. We apply a computational methodology known as an agent-based model (ABM) to simulate cellular behavior as automata. Our ABM is a tissue maintenance model where agents modify tissue density to sustain a global mean and variance to represent the cyclic turnover of ECM. Agents traverse and interact with high fidelity architecture obtained through micro computed tomography (microCT) of mouse lung tissue. The properties of the ABM are validated to microCT of fibrotic mouse lung tissue. We find that increasing cell density is sufficient for fibrogenesis, but that the lung architecture led to more tissue deposition. Our model suggests that lung structure is a relevant contributor to the pathogenesis of IPF.