Abstract:
We present a computational model that successfully captures the cell
behaviors that play important roles in 2-D cell aggregation. A virtual
cell in our model is designed as an independent, discrete unit with a
set of parameters and actions. Each cell is defined by its location,
size, rates of chemoattractant emission and response, age, life cycle
stage, proliferation rate and number of attached cells. All cells are
capable of emitting and sensing a chemoattractant chemical, moving,
attaching to other cells, dividing, aging and dying. We validated and
fine-tuned our in silico model by comparing simulated 24-h aggregation
experiments with data derived from in vitro experiments using PC12
pheochromocytoma cells. Quantitative comparisons of the aggregate
size distributions from the two experiments are produced using the
Earth Mover's Distance (EMD) metric. We compared the two size
distributions produced after 24 h of in vitro cell aggregation and the
corresponding computer simulated process.
Iteratively modifying the model's parameter values and measuring the
difference between the in silico and in vitro results allow us to
determine the
optimal values that produce simulated aggregation outcomes closely
matched to the PC12 experiments. Simulation results demonstrate the
ability of the model to recreate large-scale aggregation behaviors
seen in live cell experiments.
