Extrinsic Fluctuations in the p53 Cycle

Manuel Eduardo Hernández-García, Mariana Gómez-Schiavon, Jorge Velázquez-Castro
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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.
p53 周期的外部波动
波动是生物系统所固有的,产生于分子相互作用的随机性,影响着系统行为、稳定性和鲁棒性的各个方面。这些波动可分为源于系统固有结构和动力学的内在波动和源于温度变化等外部因素的外在波动。然而,研究这些影响给计算带来了巨大挑战。在这项研究中,我们采用一种尚未探索的方法,利用常微分方程来分析外在波动对随机系统的影响,而不是求解带有随机参数的主方程。通过将温度波动纳入反应速率,我们探索了外在因素对系统动力学的影响。我们构建了一个主方程,并计算了前两个时刻的动力学方程,与直接求解化学主方程相比,计算效率更高。我们应用这种方法分析了一个生物振荡器,重点是 p53 模型及其对外部温度波动的响应。我们的发现强调了外在波动对生物系统振荡性质的影响,振荡行为的改变取决于外在波动的特征。这项研究为了解外在波动对生物振荡的影响提供了宝贵的见解,并强调了在更复杂的系统中考虑外在波动以防止与健康问题相关的不必要情况发生的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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