Nonlinear dynamics of cell cycles with stochastic mathematical models

Melnik, R.V.N., Wei, X.L., Moreno-Hagelsieb, G.

Journal of Biological Systems, 17(3), 425-460, 2009  


Cell cycles are fundamental components of all living organisms and their systematic studies extend our knowledge about the interconnection between regulatory, metabolic, and signaling networks, and therefore open new opportunities for our ultimate efficient control of cellular processes for disease treatments, as well as for a wide variety of biomedical and biotechnological applications. In the study of cell cycles, nonlinear phenomena play a paramount role, in particular in those cases where the cellular dynamics is in the focus of attention. Quantification of this dynamics is a challenging task due to a wide range of parameters that require estimations and the presence of many stochastic effects. Based on the originally deterministic model, in this paper we develop a hierarchy of models that allow us to describe the nonlinear dynamics accounting for special events of cell cycles. First, we develop a model that takes into account fluctuations of relative concentrations of proteins during special events of cell cycles. Such fluctuations are induced by varying rates of relative concentrations of proteins and/or by relative concentrations of proteins themselves. As such fluctuations may be responsible for qualitative changes in the cell, we develop a new model that accounts for the effect of cellular dynamics on the cell cycle. Finally, we analyze numerically nonlinear effects in the cell cycle by constructing phase portraits based on the newly developed model and carry out a parametric sensitivity analysis in order to identify parameters for an efficient cell cycle control. The results of computational experiments demonstrate that the metabolic events in gene regulatory networks can qualitatively influence the dynamics of the cell cycle.