Computational investigation of epithelial cell dynamic phenotype in vitro

Table 1 ISEA CELL axioms and consequences of dysregulated CELL actions.

Axiom	Precondition	Action	Dysregulated action	Observed morphological changes
1	CELLS only	DIE	Do nothing	None (p > 0); unchecked growth (p = 0)
2	LUMINAL SPACE only	DIE	Do nothing	None (p ≥ 0)
3	MATRIX only	DIVIDE non-directionally	Do nothing	None (p ≥ 0)
4	1 CELL and LUMINAL SPACES; no MATRIX	Produce and deposit MATRIX	Do nothing	None (p ≥ 0)
5	≥ 2 CELLS and LUMINAL SPACE; no MATRIX	DIE	Do nothing	Increased CELL population; nested CELL CLUSTERS in CYST LUMEN (p < 1)
6	≥ 1 CELL and MATRIX; no LUMINAL SPACE	DIVIDE directionally	DIVIDE in a random direction	Increased CELL population; nested CELL CLUSTERS in CYST LUMEN (p < 1)
7	MATRIX and ≥ 2 LUMINAL SPACES; no CELLS	DIVIDE directionally	DIVIDE in a random direction	None (p ≥ 0)
8	CELLS, MATRIX, and ≥ 2 adjacent LUMINAL SPACES	DIVIDE directionally	N/A	N/A
9	2 CELLS, MATRIX, and LUMINAL SPACE; POLARIZING condition*	POLARIZE	N/A	N/A
10	DEPOLARIZING condition^†	DEPOLARIZE	N/A	N/A
11	All other configurations	Do nothing	N/A	N/A
12	POLARIZING condition; 1 MATRIX	Move and replace the neighboring MATRIX	Do nothing	Frequently irregular, nonconvex CYST shape (p < 1)

Each axiom's precondition takes into consideration the six objects adjacent to the decision-making CELL. In dysregulated state, the normal CELL action applies with probability p; the dysregulated CELL action applies with probability 1 - p. Exploration of Axioms 8–11 was beyond the scope of this study. Axiom 12 is used only by ISEA2.
* Two CELL neighbors separate MATRIX on one side from LUMINAL SPACE on the other side. ^†A POLARIZED CELL has noncontiguous MATRIX neighbors.

ISSN: 1742-4682