Extrinsic Fluctuations in the p53 Cycle

TL;DR

This paper investigates how external temperature fluctuations influence the behavior of the p53 biological oscillator using a novel moment-based approach, revealing significant effects on oscillation amplitude and frequency.

Contribution

It introduces an efficient method to analyze extrinsic fluctuations in stochastic systems via moment equations, applied here to the p53 cycle.

Findings

Extrinsic fluctuations increase oscillation amplitude.

Temperature fluctuations alter oscillation frequency.

The method offers computational advantages over traditional stochastic simulations.

Abstract

Fluctuations are inherent to biological systems, arising from the stochastic nature of molecular interactions, and influence various aspects of system behavior, stability, and robustness. These fluctuations can be categorized as intrinsic, stemming from the system's inherent structure and dynamics, and extrinsic, arising from external factors, such as temperature variations. Understanding the interplay between these fluctuations is crucial for obtaining a comprehensive understanding of biological phenomena. However, studying these effects poses significant computational challenges. In this study, we used an underexplored methodology to analyze the effect of extrinsic fluctuations in stochastic systems using ordinary differential equations instead of solving the Master Equation with stochastic parameters. By incorporating temperature fluctuations into reaction rates, we explored the impact of extrinsic factors on system dynamics. We constructed a master equation and calculated the equations for the dynamics of the first two moments, offering computational efficiency compared with directly solving the chemical master equation. We applied this approach to analyze a biological oscillator, focusing on the p53 model and its response to temperature-induced extrinsic fluctuations. Our findings underscore the impact of extrinsic fluctuations on the nature of oscillations in biological systems, with alterations in oscillatory behavior depending on the characteristics of extrinsic fluctuations. We observed an increased oscillation amplitude and frequency of the p53 concentration cycle. This study provides valuable insights into the effects of extrinsic fluctuations on biological oscillations and highlights the importance of considering them in more complex systems to prevent unwanted scenarios related to health issues.