Movement in a confluent 3t3 monolayer and the causes of contact inhibition of overlapping

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Abstract
The existence of contact inhibition of nuclear overlapping (monolayering) has previously been interpreted to mean that intercellular contact locally inhibits the cell’s locomotory apparatus and hence that cells in a confluent monolayer should be immobilized. Garrod & Steinberg, however, observed gross movements and exchanging of nuclear nearest neighbour relationships in a confluent monolayer of chick epithelial-like cells. Data presented in the present report reveal that similar movements occur in confluent monolayers of mouse 3T3 fibroblasts, previously shown to display contact inhibition of speed, contact inhibition of overlapping, and postconfluence inhibition of cell division. Cytoplasmic boundaries frequently could not be resolved in the present study. However, during a 22-day period, more than one third of originally adjacent pairs of nuclei became separated by 1·5 intervening nuclei, and their average distance of separation increased more than 2-fold. Also, each nucleus was displaced, on average, more than one mean cell diameter in a random direction. These indications of gross cellular movements were seen during the stationary density phase of perfused culture, as well as during the doubling of cell density which occurs after confluence but before the stationary phase. If the intensity of cell-substratum adherence exceeds that of cell-cell adherence, this differential in adhesive strength could, by itself, produce the observed avoidance of overlapping, without invoking local inhibition of the cell’s internal ‘motor’ by contact. This differential adhesion hypothesis for contact inhibition of overlapping is consistent with the extensive movements very likely occurring in at least certain confluent monolayers. On the other hand, the probable existence of these movements seems less easily reconciled with the hypothesis that contact inhibition of overlapping results from contact-induced local paralysis of an intracellular locomotory apparatus, although this latter hypothesis is not excluded.