Inferring Growth Control Mechanisms in Growing Multi-cellular Spheroids of NSCLC Cells from Spatial-Temporal Image Data
Fig 5
Scheme of cell states and the biological processes a cell can undergo: cell cycle (including cell growth and division), migration, cell death (apoptosis and necrosis) and lysis.
Left panel: A cycling cell grows by occupying two neighboring lattice sites after a fraction of transitions in the cell cycle. Growing cells can push a certain number of cells aside. Cells can migrate by hopping from one lattice site to its neighbor lattice site. A cell dies with rate kneck and is consequently lysed with rate klys. (The schemes in the left panel are 2D for clarity; the simulations however were all in 3D). Right: All processes are modeled as Poisson processes. A cell in the cell cycle undergoes md transitions until splitting into two daughter cells. Composed of md sub-processes the cell cycle time ends up following an Erlang distribution. Increasing md will lead to sharper cell cycle distributions. A cell transitions from one cell cycle state (CCS) to the next with rate kdiv,m. If a cell is in state mg it will grow. If it is in state md it will divide into 2 daughter cells during the next transition. Furthermore, the 2 daughter cells will either enter the first CCS proportional to probability pdiv or become quiescent (G0) proportional to probability 1 − pdiv. A cell in quiescence can reenter the cell cycle with rate kre and probability pre. Table 2 indicates how all transition rates and probabilities are calculated for models 1–4.