Dysregulation of Axiom 5 or 6 has a disruptive effect on ISEA CULTURE morphology in a severity-dependent manner. Axiom 5 dictates ANOIKIS (which maps to a form of cell death) when the CELL in its neighborhood has at least two CELLS and LUMINAL SPACE but no MATRIX. In simulations dysregulating Axiom 5, CELLS evaded ANOIKIS (by doing nothing) with a parameter-controlled probability, p, when Axiom 5's precondition was met. Axiom 6 dictates oriented CELL DIVISION when the CELL has at least one CELL and MATRIX but no FREE SPACE. When Axiom 6 was dysregulated, CELLS carried out disoriented CELL DIVISION: the CELL copy replaced a randomly selected MATRIX neighbor without regard for CELL neighbor number. Shown are CULTURE images and corresponding morphology index values after 50 simulation cycles of growth. One simulation cycle maps to 12 h in vitro. Each object is represented as a hexagon: POLARIZED CELL (red), UNPOLARIZED CELL (gray), MATRIX (white), and LUMINAL SPACE (black). One CELL width maps to 10 μm. (A) Axiom 5 dysregulation caused progressively disorganized CULTURE formations. (B) Axiom 6 dysregulation showed a similarly severity-dependent effect. The changes were less prominent but nevertheless clearly aberrant in both analogues.
Kim et al. BMC Systems Biology 2009 3:122 doi:10.1186/1752-0509-3-122