Ensemble controllability of cellular oscillators

Many diseases including cancer, Parkinson's disease and heart diseases are caused by loss or malfunction of regulatory mechanism of an oscillatory system. Successful treatment of these diseases might involve recovering the healthy behavior of the oscillators in the system, i.e., achieving synchrony or a desired distribution of the oscillators on their periodic orbit. In this letter, we consider the problem of controlling the distribution of a population of cellular oscillators described in terms of phase models. Different practical limitations on the observability and controllability of cellular states naturally lead to an ensemble control formulation in which a population-level feedback law for achieving a desired distribution is sought. A systems theoretic approach to this problem leads to Lyapunov- and LaSalle-like arguments, from which we develop our main contribution, novel necessary and sufficient conditions for the controllability of phase distributions in terms of the Fourier coefficients of the phase response curve. Since our treatment is based on a rather universal formulation of phase models, the results and methods proposed in this letter are readily applicable to the control of a wide range of other types of oscillating populations, such as circadian clocks, and spiking neurons.