A nested bistable module within a negative feedback loop ensures different types of oscillations in signaling systems

• Autores: Marrone, Juan Ignacio; Sepulchre, Jacques Alexandre; Ventura, Alejandra
• Año de publicación: 2023
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: MULTISTABILITY; OSCILLATORS; NONLINEAR; SYSTEMS
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

In this article, we consider a double phosphorylation cycle, a ubiquitous signaling component, having the ability to display bistability, a behavior strongly related to the existence of positive feedback loops. If this component is connected to other signaling elements, it very likely undergoes some sort of protein–protein interaction. In several cases, these interactions result in a non-explicit negative feedback effect, leading to interlinked positive and negative feedbacks. This combination was studied in the literature as a way to generate relaxation-type oscillations. Here, we show that the two feedbacks together ensure two types of oscillations, the relaxation-type ones and a smoother type of oscillations functioning in a very narrow range of frequencies, in such a way that outside that range, the amplitude of the oscillations is severely compromised. Even more, we show that the two feedbacks are essential for both oscillatory types to emerge, and it is their hierarchy what determines the type of oscillation at work. We used bifurcation analyses and amplitude vs. frequency curves to characterize and classify the oscillations. We also applied the same ideas to another simple model, with the goal of generalizing what we learned from signaling models. The results obtained display the wealth of oscillatory dynamics that exists in a system with a bistable module nested within a negative feedback loop, showing how to transition between different types of oscillations and other dynamical behaviors such as excitability. Our work provides a framework for the study of other oscillatory systems based on bistable modules, from simple two-component models to more complex examples like the MAPK cascade and experimental cases like cell cycle oscillators.
Fil: Marrone, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; Argentina
Fil: Sepulchre, Jacques Alexandre. Institut de Physique de Nice; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Ventura, Alejandra. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina