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

Summary 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.