Light-based feedback for controlling intracellular signaling dynamics.

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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.