Evidence for Long-Range Effects in Density-Dependent Inhibition of Proliferation (DDIP) in 3T3 Cells

Abstract

Nonhomogeneously seeded monolayer cultures of 3T3 cells were labelled for 6 h with 3H-TdR and the proportion of labelled cells in different parts of each culture system examined in autoradiographs. In each it was found that there is an inverse relationship between the local cell density and the proportion of labelled cells, a finding which is consistent with our previously published results with these cells, and which suggests that short-range inhibitory interactions are involved. Further analysis of the data, which is presented in this paper, shows that a correlation exists between the local labelling index and the over-all cell density in the culture, indicating the existence of long-range interactions between cells. We show that the pattern of density-dependent growth inhibition is explicable in terms of a model which considers the culture medium to be composed of two fluid compartments: a stagnant boundary layer about 12 μ in depth (the pericellular compartment), and the bulk medium (supracellular compartment). It is shown that the properties of this model are consistent with the observations for both long- and short-range cellular interaction in the limitation of proliferation in monolayer cultures.