Time evolution of microenvironment around cells regulated by the secretion activity and culture density of the cells

Cells are the minimum unit of function for a living body. Cells are in a dynamic equilibrium state with mutually interacting with the microenvironment surrounding the cells. We focused on whether cellular responses also could be regulated in the interaction of cells with the other cells and/or the microenvironment of them. Here, we try to uncover the mechanism for the macrophages to acquire a stable response at the high cell density through simulations of the way for cell-cell communication via IFN-β. As a result, the extracellular concentration of IFN-β increased rapidly, and uniformly reached the effective concentration in any place in high-density culture condition. On the other hand, the local concentration of IFN-β in the low-density culture condition could rise transiently but easily decreased by diffusion, indicating that it was hard to reach the effective concentration in the most area. The cell density-dependent differences in IFN-β field formation were also shown to have a decisive effect on the stability of cellular responses from the population of cells. Collectively, we successfully demonstrated that the cells themselves dynamically form the surrounding microenvironment to regulate their own activity.