ABSTRACT
Using intuitive arguments, several investigators have proposed that the relative strengths of adhesion of cell to cell and of cell to substratum could determine whether or not monolayering – and specifically contact inhibition of cell overlapping – will occur. In the present communication, these ‘strengths of adhesion’ are given precise physical definitions, and the adhesive relationships which would promote spontaneous cell monolayering are rigorously derived, using the thermodynamic approach embodied in the differential adhesion hypothesis. This analysis verifies that contact inhibition of overlapping could, in principle, be a result solely of differential adhesion. In addition, it is demonstrated that for homogeneous populations of uniform cells cultured on a solid, uniform substratum, eleven distinct equilibrium configurations (cell population morphologies) could be generated merely by varying the relative values of cell-to-cell and cell-to-substratum adhesiveness. Most of these configurations have been observed previously in actual cell cultures.
This last inhibition has also been called density-dependent inhibition of replication (Stoker & Rubin, 1967), cell cycle inhibition (Macieira-Coelho, 1967a), and topoinhibition (Dulbecco, 1970). Direct scrutiny of cells undergoing this inhibition in time-lapse films has failed to reveal any immediate effect of either intercellular contacts or of high local cell density on individual cell generation times (Martz & Steinberg, 1972). Moreover, a connexion between this inhibition of cell division and contact inhibition of speed or of overlapping has not been found when looked for (Macieira-Coelho, 19676; Njeuma, 1971; Martz, 1973; Gail, 1973). Because this inhibition is correlated with the confluence of a cell culture, we prefer to describe it by the operational term ‘postconfluence inhibition of cell division’ (Martz & Steinberg, 1972).
More consistent symbols for W(agg.) and W(att.) would be 
and 
, respectively, which designate the work of formation from the reference state (acc= ac8= o) in the presence of culture medium. The symbols W(agg.) and W(att.) are used because of their heuristic value.
