Processing pulsatile inputs in cell signaling: when to expect a frequency preference

VENTURA, ALEJANDRA C.

Puerto Madryn

Workshop; Workshop Statistical physics in biological networks; 2020

General Sarmiento National University

Cellular processes are frequently regulated by signals whose activity change over time, often in a pulsatile manner, in the form of either periodic oscillations or stochastic pulses. Pulsatile signals are characterized by the amplitude and duration of the pulses, and by the time between consecutive pulses. Changes in these properties can potentially lead to different cellular responses. In this work we study which properties determine the existence of an optimal activating signal for a signaling target. Particularly, we focus on the frequency of the activating signal, for doing so we consider dose-conserved pulsatile inputs, meaning that the amplitude of the pulses is varied along with frequency to conserve input dose. When a pulsatile signal stimulates a (simple) signaling component, an initial, transient response is induced, later a stationary periodic behavior is achieved. This last phase is obtained whenthe stimulation lasts for a long time compared with the timescale of the signaling  component. Several articles in the literature have looked for motifs and conditions leading to frequency preference. However, all of them focus on the stationary response. In this work we focus on what we call transient frequency preference (TFP), meaning with this that there is a maximum in the frequency-response curve when the response is measured in a time window within the transient phase.