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.

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