Multi-Agent Simulation of Self-Organizing Behaviors of Alveolar Cells In Vitro

We present an agent-based model of cultured lung alveo- lar type II (AT II) cells and simulation results that provide early in- sight into generative principles underpinning alveolar morphogenesis in 3D cell cultures. We also describe a supporting framework and system-level agents that manage simulation experiments. The AT II cell-mimetic analogue comprises discrete components that represent cells and basic parts composing cell cultures. Cells are represented as quasi-autonomous agents that act based on decision logic and a set of operating principles articulated as axioms. By adhering strictly to those principles, cell agents self-organize and develop into multi-cell structures that resemble alveolar-like cysts in vitro. While it is pre- mature to assign a specific biological mapping to the in silico operat- ing principles, the findings enforce the idea that complex morphoge- netic phenomena are a consequence of adherence to a small set of epigenetic principles. We expect more advanced adaptations will provide a rigorous platform to unravel the mechanistic bases of al- veolar development and regeneration.