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核糖体与信使核糖核酸相互作用的动力学及生长速率影响 于……(原文此处不完整)

Dynamics and growth rate implications of ribosomes and mRNAs interaction in .

作者信息

Phan Tin, He Changhan, Loladze Irakli, Prater Clay, Elser Jim, Kuang Yang

机构信息

School of Mathematical and Statistical Sciences, Arizona State University, Tempe, AZ 85287, USA.

Division of Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87544, USA.

出版信息

Heliyon. 2022 Jun 28;8(7):e09820. doi: 10.1016/j.heliyon.2022.e09820. eCollection 2022 Jul.

Abstract

Understanding how cells grow and adapt under various nutrient conditions is pivotal in the study of biological stoichiometry. Recent studies provide empirical evidence that cells use multiple strategies to maintain an optimal protein production rate under different nutrient conditions. Mathematical models can provide a solid theoretical foundation that can explain experimental observations and generate testable hypotheses to further our understanding of the growth process. In this study, we generalize a modeling framework that centers on the translation process and study its asymptotic behaviors to validate algebraic manipulations involving the steady states. Using experimental results on the growth of under C-, N-, and P-limited environments, we simulate the expected quantitative measurements to show the feasibility of using the model to explain empirical evidence. Our results support the findings that cells employ multiple strategies to maintain a similar protein production rate across different nutrient limitations. Moreover, we find that the previous study underestimates the significance of certain biological rates, such as the binding rate of ribosomes to mRNA and the transition rate between different ribosomal stages. Furthermore, our simulation shows that the strategies used by cells under C- and P-limitations result in a faster overall growth dynamics than under N-limitation. In conclusion, the general modeling framework provides a valuable platform to study cell growth under different nutrient supply conditions, which also allows straightforward extensions to the coupling of transcription, translation, and energetics to deepen our understanding of the growth process.

摘要

了解细胞在各种营养条件下如何生长和适应是生物化学计量学研究的关键。最近的研究提供了经验证据,表明细胞在不同营养条件下使用多种策略来维持最佳蛋白质产生率。数学模型可以提供坚实的理论基础,用以解释实验观察结果并生成可检验的假设,从而加深我们对生长过程的理解。在本研究中,我们推广了一个以翻译过程为核心的建模框架,并研究其渐近行为以验证涉及稳态的代数运算。利用在碳、氮和磷限制环境下的生长实验结果,我们模拟预期的定量测量,以展示使用该模型解释经验证据的可行性。我们的结果支持了细胞采用多种策略在不同营养限制条件下维持相似蛋白质产生率的发现。此外,我们发现先前的研究低估了某些生物学速率的重要性,例如核糖体与信使核糖核酸的结合速率以及不同核糖体阶段之间的转换速率。此外,我们的模拟表明,细胞在碳和磷限制条件下使用的策略导致总体生长动态比在氮限制条件下更快。总之,通用建模框架为研究不同营养供应条件下的细胞生长提供了一个有价值的平台,这也允许直接扩展到转录、翻译和能量学的耦合,以加深我们对生长过程的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1520/9254350/8dfa90263a7c/gr001.jpg

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