Figure 1. Relationships between in silico AT II analogues and AT II cells in culture.

To distinguish simulation components and characteristics from in vitro counterparts, we use small caps when referring to the former. All systemic in vitro attributes are consequences of AT II cells interacting with each other and components of their environment. To create the analogue's mechanisms, we focused on the cell level, because cells are the system's primary functional units. We specified quasi-autonomous cell components that interact with all components in their adjacent environment. We required that each component map clearly to an in vitro counterpart. To enable remodeling of cell clusters into stable alveolar-like cysts, we used iterative analogue refinement to discover a set of axiomatic operating principles to which cells tightly adhered. The sum of local component interactions during execution represented the analogue's mechanisms. They gave rise to observable, measurable, systemic phenomena. A degree of validation was achieved when a set of in silico attributes achieved a prespecified Similarity Measure: i.e., measures of analogue attributes were within a prespecified range of corresponding measures of in vitro attributes. Upon validation, we could hypothesize that a semiquantitative mapping existed between in silico causal events and in vitro causal events. We could also hypothesize that the set of in silico operating principles had a biological counterpart.