Sensing and making sense of fluctuating cellular states

The self-organisation of cells into complex tissue relies on the tight regulation of cellular behavior. Typically, the regulation of cell decisions is attributed to pathways controlling the concentration of molecular species in response to intrinsic or extrinsic signals, such as in gene regulatory networks. Here, by contrast, we show in the paradigmatic example of cell death that cells manipulate how fluctuations propagate across spatial scales to regulate cellular behavior. Specifically, we find that the feedback between molecular and mesoscopic organelle fluctuations gives rise to a quasi-particle degree of freedom whose intriguing kinetic properties construct a kinetic low-pass filter of time-dependent concentrations of signaling molecules. This allows cells to distinguish between fast fluctuations and slow, biologically relevant, changes in environmental signals. We demonstrate an order of magnitude effect of this phenomenon on the quality of the cell death decision and validate our predictions experimentally by dynamically perturbing the intrinsic apoptosis pathway. Our work reveals a new mechanism of cell fate decision making.