Modeling the effect of exogenous calcium on keratinocyte and HaCat cell proliferation and differentiation using an agent-based computational paradigm.

In this study we sought to develop a computational modeling paradigm in order to describe the influence of calcium on normal and transformed keratinocyte proliferation and differentiation. Keratinocytes and HaCat cells were grown in monolayer cultures with low and physiologic calcium concentrations, and levels of proliferation and involucrin expression were assessed. Both types of cells grew as monolayers under a low-calcium environment, and stratified in media with physiologic levels of calcium. However, keratinocytes were more proliferative in low rather than physiologic levels of calcium, whereas the opposite was true for HaCat cells. Normal keratinocytes differentiated as calcium levels increased. HaCat cells showed little differentiation at any calcium concentration. However, while the computer simulation could be modified to describe the effect of calcium on the growth of normal keratinocytes, our findings did not support the hypothesis that simply "turning off" the ability of HaCat cells to differentiate would account for the growth characteristics of these transformed cells. This demonstrates the application of computational modeling to hypothesis testing in biological systems.