Dynamics of cellular growth.

The assumption that prompted the studies reported in this paper was that the unsatisfactory state of our knowledge on the regulation of cellular growth might derive from the reductionistic approach used to investigate it. Thus an analysis of cellular growth which applied concepts derived from systems dynamics was undertaken. First of all a dynamic model of cellular growth has been constructed. It has the following features: the levels of DNA, ribosomes and proteins are the defining levels; cellular growth is expressed by a close loop in which the level of ribosomes per genome and, indirectly, the level of proteins per genome are stabilized around goal values by the action of negative feed backs. The validity of the model has been tested by its ability to predict the growth kinetics of a real system (exponentially growing Neurospora cells). The simulated growth has been found to reproduce with great accuracy that of Neurospora cells. A slightly modified model, which takes into consideration also the degradation of ribosomes and of proteins, is shown to predict with accuracy the dynamics of growth of both growing and resting fibroblasts. These latter results suggest that the rates of macromolecular turnovers play a central role in the control of proliferation of mammalian cells: the condition of zero growth seems to be achieved when the rate of synthesis and the rate of degradation of proteins are the same. The possibility is discussed that the model indicates a unifying hypothesis of the mode of action of growth controlling conditions (hormones, growth factors, contact inhibition).