Light-based feedback for controlling intracellular signaling dynamics

Abstract

The ability to apply precise inputs to signaling species in live cells would be transformative for interrogating and understanding complex cell signaling systems. Here, we report a method for applying custom signaling inputs using feedback control of an optogenetic protein-protein interaction. We apply this strategy for perturbation of protein localization and phosphoinositide 3-kinase activity, generating time-varying signals and clamping signals to buffer against cell-to-cell variability or pathway activation changes.