Cellular Adaptation to Signal Fluctuations as Learning

Cells represent one of the most fundamental units of life. Underlying their robust performance against environmental variability, such as temporal fluctuations of chemical signals, between different cell types, is a dynamical interrelation between the two components of an intracellular pathway: a gene-regulatory network and its upstream signal transducers. To understand how a single cell utilizes this feedback to self-regulate its gene-expressions, we develop a multiscale model of the pathway’s components, in which the adaptive variables responsible for signal interpretation follow a feedback-induced learning process. We then derive a macroscopic theory capturing the covariations between these components - so-called collective modes. Our theory shows how cells can achieve robust output against signal fluctuations via self-regulation rather than simple noise suppression. Such robustness corresponds to a transition from random- to structured collective modes beyond a critical adaptation rate.