Contact regulation of cell division in an epithelial‐like cell line

The rate of cell division in an epithelial‐like cell line, 1S1, was examined by time‐lapse cinemicrography. When precautions were taken to insure a sufficient nutrient supply, the number of mitoses per unit time in any given area of a confluent monolayer remained constant. This “contact regulation of cell division” resulted in a steadily decreasing frequency of mitosis per cell as the culture became crowded. With the decrease was associated a gradual change in cell shape, from maximally flattened to maximally compact, due to contact inhibition of the movement of cells across one another. When cells were removed along a line scraped on a dense culture, the cells at the edge of the scrape flattened, migrated into the vacant area, and subsequently increased their frequency of mitosis to that characteristic of non‐confluent cells. Inhibition of mitosis caused by a limitation on the nutrient supply was also reversed at a line‐scrape. These observations suggest that cell flattening promoted mitosis by causing the cell membrane to expand, thereby facilitating the uptake of nutrients. The cell membrane would thus function in the mechanism of contact regulation as a transducer, for converting the pressure of the surrounding cell population into a restraining force upon the metabolism of cell division.