TY - JOUR
T1 - Dynamics and growth rate implications of ribosomes and mRNAs interaction in E. coli
AU - Phan, Tin
AU - He, Changhan
AU - Loladze, Irakli
AU - Prater, Clay
AU - Elser, Jim
AU - Kuang, Yang
N1 - Publisher Copyright:
© 2022 The Author(s)
PY - 2022/7
Y1 - 2022/7
N2 - 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 E. coli 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.
AB - 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 E. coli 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.
KW - Cell growth
KW - Growth rate hypothesis
KW - Inactive ribosomes
KW - Mathematical analysis
KW - Model formulation
KW - Model validation
KW - Translation dynamics
UR - http://www.scopus.com/inward/record.url?scp=85133211140&partnerID=8YFLogxK
U2 - 10.1016/j.heliyon.2022.e09820
DO - 10.1016/j.heliyon.2022.e09820
M3 - Article
AN - SCOPUS:85133211140
SN - 2405-8440
VL - 8
JO - Heliyon
JF - Heliyon
IS - 7
M1 - e09820
ER -