Figure 4

Dysregulation of Axiom 5 ( ANOIKIS ) and its effect on ISEA CULTURE growth and morphology. Axiom 5 dictates CELL DEATH when a CELL has in its neighborhood at least two CELLS and LUMINAL SPACE but no MATRIX. With a parameter-controlled probability, p, CELLS evaded ANOIKIS (by doing nothing) when Axiom 5's precondition was met. Doing so caused distinct changes in growth and structural characteristics of the EMBEDDED CULTURE. (A) CELL CULTURE growth rate increased monotonically with the severity of dysregulation. CULTURE growths at six levels of dysregulation are shown. (B) Disrupting operation of Axiom 5 resulted in the formation of progressively aberrant MULTICELL structures, as indicated by the numeric scale. Higher values indicate a more disorganized morphology. Dysregulation had no observable effect on CULTURE morphology in the early stages (~5 simulation cycles) of growth. One simulation cycle maps to 12 h in vitro. The effect became progressively evident as simulation time advanced. (C-D) Axiom 5 dysregulation altered CELL DIVISION and DEATH event patterns. The changes became more evident at later times. In both simulations, the effect on CELL DEATH and DIVISION was monotonic, except when p = 0. The mean occurrence of CELL DIVISION and DEATH fell when p = 0 (vs p = 0.8). The data are mean values of 100 Monte Carlo runs.