The relative significance of growth rate and interdivision time in the size control of cultured mammalian epithelial cells.

Genealogies of a line of mammalian epithelial cells (GPK) have been constructed from time-lapse film of monolayer cultures and measurements made of initial (post-divisional) cell size, final (pre-divisional) cell size and interdivision time (IDT). The mean initial cell volume was 2696 +/- 404 (S.D.) micron3, the mean final volume was 5247 +/- 696 micron3 and the mean IDT was 985 +/- 84 min. Cell size regulation must be by modulation of either the growth rate or the length of the growth period. Increase in size was strongly correlated with the average rate of growth (increase in volume per unit time) (R = 0.94, P much less than 0.001), whilst no correlation was found between increase in size and IDT. Although a negative correlation was found between initial volume and IDT (P less than 0.02), this appeared to be due to differences in IDT between sister cells being correlated with differences in their initial volumes (P less than 0.02), as indicated by the lack of correlation between mean sister IDT and mean sister initial volume. The regulatory effect of growth rate was demonstrated by a negative correlation between growth rate and the initial volume of the cell (P less than 0.005), which is independent of differences between siblings. The mean growth rate of sibling cells was found to be negatively correlated with both the maternal growth rate (P less than 0.01) and the maternal volume increase (P less than 0.005). This implies that the growth rate of division products (which manifest similar growth rates) is influenced by the growth of the progenitor cell.