Systems Modeling of Alveolar Morphogenesis In Vitro

We present a pulmonary alveolar epithelial cell model and its simulation results aimed to provide mechanistic insight into biological principles that underlie alveolar morphogenesis in vitro. Primary human alveolar type II cells in 3D cultures have been shown to undergo processes of cell migration and aggregation to form hollow cystic structures that resemble human lung alveoli. Although various molecular factors that mediate alveolization have been identified, little is known about biological principles that drive the morphogenic processes. To help elucidate the operating principles governing the morphogenic behavior of pulmonary epithelial cells, we have developed an agent-based model of alveolar cells in culture. The model system comprises discrete components that represent individual cells and different elements of the extracellular environment. Individual cells are represented as independent agents that act based on a set of axioms (principles) that govern their interaction with the surroundings. Simulation of alveolar cell cultures confirms that the model is capable of generating phenotypic attributes similar to those of in vitro observations. Based on the results, we hypothesize that the axioms governing simulated cell behavior have in vitro counterparts. Further interrogation and refinement of the model is expected to help unravel the causal linkages between the operating principles of cell behavior and observed systemic phenotypes.