Table 1. Targeted attributes and specifications.
1. | A: An initial small cluster of 1-4 cells divides and increases in cell number. |
S: The ISMA begins with 2-4 cells, which divide after cycleCounter reaches 0. | |
2. | A: All cells polarize by the second day of growth. |
S: Cells change state to polarized after polarCounter reaches zero. | |
3. | A: One or more lumens develop by the second day of growth. |
S: Cells within cysts form lumens after cells polarize. | |
4. | A: A multilayer of cells separates multiple lumens. |
S: Cells only form lumens when they and their neighbors do not already contact lumen. After a lumen has formed, all neighboring cells contact a single lumen. | |
5. | A: Cells can undergo apoptosis whether or not they contact the extracellular matrix. |
S: Cells die with specified probability. That value is larger for cells not in contact with matrix. | |
6. | A: The increase in cell number over time is similar that shown in Figure 2, leveling off at day 6. |
S: When lumen size reaches a critical value, a mechanism causes cells to stabilize. | |
7. | A: The increase in cyst size over time is similar to that shown in Figure 2. |
S: Cyst size is a function of cell area, cell number, and lumen size. | |
8. | A: The increase in lumen size over time is similar to that shown in Figure 2. |
S: Lumen size is a function of cell number, cyst perimeter, cell stretch, and time. | |
9. | A: Mean cell area decreases over time as shown in Figure 2, and levels off at day 6. |
S: Cells have distinct mechanisms for (effectively) calculating TA before and after stabilization. | |
10. | A: The decrease in the ratio of cellular to cyst area over time is similar to that in Figure 2, decreasing faster during days 2-6. |
S: Cell area, lumen size, and cyst size must be measurable and if these quantities validate, then so must the ratio of cellular to cyst area. | |
11. | A: The percentage of single-lumen, multiple lumen, and SLSL cysts each day is similar to that in Figure 3. |
S: When cells lack lumen contact, they can create new lumens. Lumen creation occurs at the site of previous cell division. Lumens can expand and merge. Cells that have stabilized cannot create a new lumen. | |
12. | A: The percentage of cysts with apoptotic cells each day is similar to that observed in [9]. |
S: Cells shrink after beginning to die. The percentage of cysts with dying cells is calculated as in vitro. | |
13. | A: When the orientation of the cell axis of division is disrupted or reversed, the percentage of normal cysts is reduced as observed in [6]. |
S: Cells orient their axis of division toward the center of prior division or toward the center of the lumen. Axis orientation can be randomized and reversed. |
MDCK cells and cysts are the referent. The model system is called an in silico MDCK analogue (ISMA). A: a targeted attribute; S: an ISMA specification. All listed attributes were achieved. The early version of the ISMA achieved TAs 1-4, but was falsified by the quantitative data. The refined ISMA achieved all TAs except 11, which was achieved by both the LS and the TS ISMAs.