Denial, acceptance, and loss of cell polarization for a stochastic model of positive feedback

Abstract

Positive feedback plays a key role in the ability of signaling molecules to form highly localized clusters in cells. What prevents positive feedback from amplifying inevitable biological noise when an un‐clustered “off” state is desired? And, what limits the spread of clusters when an “on” state is desired? Here, we show that a minimal positive feedback circuit provides the general principle for both suppressing and amplifying noise: below a critical density of signaling molecules, clustering switches off; above this threshold, highly localized clusters are recurrently generated. Clustering occurs only in the stochastic regime, suggesting that finite sizes of molecular populations cannot be ignored in signal transduction networks. Regulating the density of signaling molecules provides a simple mechanism for a positive feedback circuit to robustly switch between clustered and un‐clustered states. The intrinsic ability of positive feedback both to create and suppress clustering is a general mechanism that could operate within diverse biological networks to create dynamic spatial organization.