Noise Induces the Population-Level Entrainment of Incoherent, Uncoupled Intracellular Oscillators

Intracellular oscillators entrain to periodic signals by adjusting their phase and frequency. However, the low copy numbers of key molecular players make the dynamics of these oscillators intrinsically noisy, disrupting their oscillatory activity and entrainment response. Here, we use a combination of computational methods and experimental observations to reveal a functional distinction between the entrainment of individual oscillators (e.g., inside cells) and the entrainment of populations of oscillators (e.g., across tissues). We demonstrate that, in the presence of intracellular noise, weak periodic cues robustly entrain the population averaged response, even while individual oscillators remain un-entrained. We mathematically elucidate this phenomenon, which we call stochastic population entrainment, and show that it naturally arises due to interactions between intrinsic noise and nonlinear oscillatory dynamics. Our findings suggest that robust tissue-level oscillations can be achieved by a simple mechanism that utilizes intrinsic biochemical noise, even in the absence of biochemical couplings between cells. [Display omitted] •Intracellular oscillators often need to entrain to periodic stimuli•However, biochemical noise can disrupt the entrainment of individual oscillators•We show that population averages of noisy uncoupled oscillators entrain robustly•This may explain how noisy peripheral clocks entrain nicely at the tissue level Gupta et al. show that intrinsic biochemical noise can interact with dynamic nonlinearities to cause entrainment of the population mean of uncoupled intracellular oscillators, even though these oscillators may not be individually entrained. They call this effect stochastic population entrainment (SPE), and they demonstrate it both theoretically and computationally.