Sensing and making sense of fluctuating cellular states

The maintenance of intact tissues relies on precise cellular decision-making despite strongly fluctuating extrinsic cues. These decisions involve processes on vastly different scales, from molecules to organelles and cells in tissues. How can cells manipulate the propagation of fluctuations across these scales to perform biological function? Here, we show how the non-equilibrium interplay between microscopic and mesoscopic dynamics leads to a kinetic low-pass filter facilitating precise sensing of fluctuating cellular states. Specifically, we find that the interplay between molecular and organelle dynamics gives rise to a single, collective degree of freedom. We show that this degree of freedom exhibits rich dynamical behaviour showing different kinetics on different temporal scales and thereby leading to the suppression of fast fluctuations. We demonstrate our findings in the context of the metabolic regulation of cell death via the interplay of Bax protein dynamics with rapid mitochondrial fusion and fission and find an order of magnitude effect on the error rate of the cell death decision. Our work shows paradigmatically how biological function relies on the non-equilibrium integration of processes on different spatial scales to control and respond to fluctuations.