Theory of frequency response of mechanically driven cardiomyocytes

We theoretically predict and compare with experiments, transitions from spontaneous beating to dynamical entrainment of cardiomyocytes induced by an oscillating, external mechanical probe. In accord with recent experiments, we predict the dynamical behavior as a function of the probe amplitude and frequency. The theory is based on a phenomenological model for a non-linear oscillator, motivated by acto-myosin contractility. The generic behavior is independent of the detailed, molecular origins of the dynamics and, consistent with experiment, we find three regimes: spontaneous beating with the natural frequency of the cell, entrained beating with the frequency of the probe, and a "bursting" regime where the two frequencies alternate in time. We quantitatively predict the properties of the "bursting" regime as a function of the amplitude and frequency of the probe. Furthermore, we examine the pacing process in the presence of weak noise and explain how this might relate to cardiomyocyte physiology.