A molecular basis for indiscriminate and selective cell adhesion.

When cells of different type are intermixed they will adhere to one another indiscriminately. In mixed aggregates of o.th-incubation-day fibroblasts and I2th-day liver cells from chick embryos, the liver cells accumulated as groups which moved at random relative to the surrounding fibroblasts; groups of liver cells were liable to migrate from the interior to occupy the surface. Quantitative estimations of the effect of temperature on the rate of reaggregation of dissociated fibroblast cells, using a turbidimetric method, indicated that the rate was controlled by a chemical reaction. The energy of activation calculated for this reaction was 21-i kcal/mole. The significance of this value is discussed in relation to values associated with other kinds of reactions. The indiscriminate adhesions formed between the unlike cells allowed them to move relative to one another, whereas the adhesions (selective) formed between like cells, when by chance they made contact, did not. Thus the aggregates of like cells increased in extent and the inherent ability of homogeneous aggregates to consolidate the intercellular bonding ensured that the process became effectively irreversible. If, as is evident, there is a basic similarity in the adhesive mechanisms of the various types of cells that exist, the question that required answering was what kind of differences could occur in the bonds to account for differential adhesiveness upon which the sorting out process depends. It is suggested that the linkage sites at the surfaces of cells move (oscillate) between two positions, the one unfavourable and the other favourable to adhesion, and the theory put forward is that differential adhesiveness is the expression of differences in the frequency of the oscillations of the otherwise equivalent linkage sites. The theory provides an explanation for the temporary nature of indiscriminate adhesion allowing the movement of unlike cells in contact relative to one another and the more permanent nature of selective adhesions responsible for the consolidation of like cells in their appointed territories.