Proliferation of anchorage-dependent contact-inhibited cells: I. Development of theoretical models based on cellular...

We report the development of new class of discrete models that can accurately describe the contact-inhibited proliferation of anchorage-dependent cells. The models are based on cellular automata, and they quantitatively account for contact inhibition phenomena occurring during all stages of the proliferation process: (a) the initial stage of "exponential" growth of cells without contact inhibition; (b) the second stage where cell colonies form and grow with few colony mergings; and (c) the final stage where proliferation rates are dominated by colony merging events. Model prediction are presented and analyzed to study the complicated dynamics of large cell populations and determine how the initial spatial cell distribution, the seeding density, and the geometry of the growth surface affect the observed proliferation rates. Finally, we present a model variant that can simulate contact-inhibited proliferation of asynchronous cell populations with arbitrary cell cycle-time distribution. The latter model can also compute the percentage of cells that are in a specific phase of their division cycle at a given time.