In order to determine whether the collective movement of the cells influences their phenotypic change we created an alternative version of the model in which the migration of the cells was not Temozolomide constrained by the cell density. The bistability of phenotypic states and the capacity of density sensing were identical in the two versions of the model. In order to study the effect of local cell density on the phenotypic fluctuation we integrated the bistability of phenotypic transition in individual cells with the agent-based model simulating the pattern formation. We simulated the bistable phenotype transition as a process of ����production���� of the new phenotype ����high P����with sigmoid kinetics described by the Hill function and a setback to the ����low P���� phenotype that followed linear kinetics. The non-linear production and linear degradation together ensure the capacity of dynamic bistable behaviour for every cell. We assume that during the in silico experiment all cells tend to a final equilibrium of ����high P���� and ����low P����phenotypes of approximately 3 to 1, as observed in living cell experiments. A cell in the model was considered ����high P���� if the actual production rate of P was higher than the rate at the inflection point of the Hill function. The control parameters in the model were: CB that determines how P production is dependent on local cell density by setting the threshold between the two stable states: noise that can be considered as a measure of stability. Typically, the noise term is defined by its relationship with the mean. In our model, the noise term was dissociated into two independent terms: intrinsic noise that depicts a white noise that occurs in any cell and is independent of the cell density and cell phenotype and context- or density-dependent noise that is a function of local cell density and the cell phenotype. Next was high in ����low P���� cells in high local density regions and in ����high P���� cells in low-density regions but low in ����low P���� cells in low local density regions and in ����high P���� cells in high-density regions. In other terms, two cells with identical levels of P are WZ4002 characterized by different level of noise i.e. different stability depending on whether they are located in high- or low-density regions. The cells in the model were able to sense the local density through the detection of the concentration of a diffusible molecule R. The value of R can be considered as a measure of local cell density. The actual concentration of R was the result of a dynamic equilibrium between the uptake and consumption by the cells and the replacement by diffusion from the culture medium.