The regulation of cell size and the control of mitosis

Abstract

There is sufficient experimental evidence to indicate that cells can regulate cell size (or nuclear-cytoplasm ratio) so that under balanced growth conditions a constant average cell size is maintained over succeeding generations. This regulation is probably effected by alterations in the timing of mitosis and/or cell division. General criteria arc established to which any model must conform which describes the regulation of cell size and mitosis. It is argued that several published models are inconsistent with these criteria. Four general classes of model are presented' which agree with these criteria. Possible underlying biological bases for the models are discussed. Mathematical descriptions of each model have been formulated allowing quantitative analysis of their regulatory properties. Different kinds of perturbations to a steady-state cell with equilibrium nuclear-cytoplasmic ratio have revealed different but characteristic response modes for different models-immediate or asymptotic or oscillatory approach back to equilibrium. The models are valid for different growth rates and growth modes. Experiments are suggested which should allow the general validity of each model to be determined. An examination of present available data does not allow a clear evaluation of any of the models since fair comparison between prediction and experiment is only valid under rigorously defined experimental conditions not so far adhered to.