Emergent robust oscillatory dynamics in the interlocked feedback-feedforward loops

Area of Science:

• Systems biology
• Computational biology
• Biophysics

Background:

• Modelling complex biological networks presents challenges in linking network structure to function and dynamics.
• Changes in network topology, such as adding or removing edges, can drastically alter cellular behavior.

Purpose of the Study:

• To investigate how adding an edge to a simple negative feedback loop creates emergent structures.
• To analyze the relationship between these emergent network structures and their resulting oscillatory dynamics.
• To explore the implications for biological systems like circadian rhythms.

Main Methods:

• Modification of a three-variable Goodwin oscillator motif by adding a new edge.
• Systematic analysis of all edge sign combinations in the emergent interlocked motif.
• Bifurcation analysis to categorize network dynamics.
• Amplitude-frequency (amp-freq) plot generation.

Main Results:

• The addition of an edge to the Goodwin motif resulted in emergent feedforward and feedback loops.
• Bifurcation analysis revealed two distinct categories of dynamics based on edge signs.
• Each category exhibited unique amplitude-frequency plots, linked to specific interlocked motif structures.
• A plant circadian model (Arabidopsis thaliana) demonstrated the role of interlocked motifs in fine-tuning oscillator amplitude and frequency.

Conclusions:

• Emergent structures in biological networks significantly influence cellular dynamics.
• Network topology dictates distinct dynamic behaviors and oscillatory properties.
• Interlocked motifs play a crucial role in the adaptation of biological oscillators to environmental cues.