Ensemble control for cell cycle synchronization of heterogeneous cell populations ?

摘要

We investigate the problem of synchronizing a population of cellular oscillators in their cell cycle. Restrictions on the observability and controllability of the population imposed by the nature of cell biology give rise to an ensemble control problem specified by finding a broadcast input based on the distribution of the population. We recently showed, that the problem can be solved by a passivity-based control law derived from the reduced phase model representation of the population. In the present paper we investigate the performance of the control law in anin silicostudy where we simulate a heterogeneous cell population with an individual-based simulation framework. Therein, the dynamics of each cell are captured by ordinary differential equations. Resampling of cellular states at cell division reflects the naturally occurring heterogeneity in a population due to uneven distribution of proteins during cytokinesis. Performance of the controller is examined in different scenarios where we vary variance during resampling against the input strength. Our results indicate a suitable range for input strength where synchrony is achieved despite the naturally occurring heterogeneity.