Non-equilibrium thermodynamics of biological signal transduction predicts conservation of entropy production rate

Tsuruyama, Tatsuaki

doi:10.1016/j.jtbi.2019.04.008

Cited by 10 publications

(9 citation statements)

References 19 publications

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“…( 5 ) and ( 6 ), we deduced that β j = − β , indicating that each molecular STR is independent of the signal molecule type number, j . Therefore, when the ST is maximized, STRs tend toward a constant value, and we predicted that the STR of each molecule in the EGFR cascade would have a similar value 21 , 22 .…”

Section: Resultsmentioning

confidence: 99%

Epidermal growth factor receptor cascade prioritizes the maximization of signal transduction

Kiso-Farnè

Tsuruyama

2022

Sci Rep

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Many studies have been performed to quantify cell signaling. Cell signaling molecules are phosphorylated in response to extracellular stimuli, with the phosphorylation sequence forming a signal cascade. The information gain during a signal event is given by the logarithm of the phosphorylation molecule ratio. The average information gain can be regarded as the signal transduction quantity (ST), which is identical to the Kullback–Leibler divergence (KLD), a relative entropy. We previously reported that if the total ST value in a given signal cascade is maximized, the ST rate (STR) of each signaling molecule per signal duration (min) approaches a constant value. To experimentally verify this theoretical conclusion, we measured the STR of the epidermal growth factor (EGF)-related cascade in A431 skin cancer cells following stimulation with EGF using antibody microarrays against phosphorylated signal molecules. The results were consistent with those from the theoretical analysis. Thus, signaling transduction systems may adopt a strategy that prioritizes the maximization of ST. Furthermore, signal molecules with similar STRs may form a signal cascade. In conclusion, ST and STR are promising properties for quantitative analysis of signal transduction.

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Section: Resultsmentioning

confidence: 99%

Epidermal growth factor receptor cascade prioritizes the maximization of signal transduction

Kiso-Farnè

Tsuruyama

2022

Sci Rep

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“…In other words, it is necessary to examine in greater detail how far the entropy-maximizing principle can be applied in a non-equilibrium system. 9 In this study, equations ( 18) and (19) were derived from the viewpoint of source-coding in information engineering. The amount of information transmissible through the chemical-reaction chain, i.e, channel capacity was represented by this entropy-time average, KS max /τ.…”

Section: Discussionmentioning

confidence: 99%

Deriving the Fluctuation Theorem for Information-Transmission Systems Using a Cyclic Chain-Reaction Sequence

Tsuruyama

2021

Preprint

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Chemical chain-reactions are pathways that can transmit information, as demonstrated by signal-transduction reactions in cell biology. In this study, we defined entropy as the logarithm of the concentration ratio of chemical species and considered the channel capacity for information transmission by maximizing the entropy. We hypothesized that the reaction chain has an orientation in which the reaction time for the reverse reaction is sufficiently long. According to this model, the logarithm of the forward and reverse transitional probability ratio was found to indicate the entropy-time average per unit reaction time, corresponding to the fluctuation theorem for thermodynamics regarding entropy production rate. This conclusion illuminates the process of signal transduction in cells and other biochemical systems and may provide insights into the relation between thermodynamic and information entropy.

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“…Normal cells expend significant energy to maintain a low entropy state. Considering the locality of the second law of thermodynamics, entropy can be divided into entropy derived from a chemical reaction and entropy produced by the diffusion of signaling molecules [ 193 , 194 ]. Organisms employ both information and energy to sustain a stable entropy that is far from thermodynamic equilibrium; high entropy implies high uncertainty or disorder in the system, meaning that more information is needed to describe it accurately [ 195 ].…”

Section: Increasing Mitochondrial Efficiencymentioning

confidence: 99%

Decreasing Intracellular Entropy by Increasing Mitochondrial Efficiency and Reducing ROS Formation—The Effect on the Ageing Process and Age-Related Damage

Poljšak,

Milisav

2024

IJMS

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A hypothesis is presented to explain how the ageing process might be influenced by optimizing mitochondrial efficiency to reduce intracellular entropy. Research-based quantifications of entropy are scarce. Non-equilibrium metabolic reactions and compartmentalization were found to contribute most to lowering entropy in the cells. Like the cells, mitochondria are thermodynamically open systems exchanging matter and energy with their surroundings—the rest of the cell. Based on the calculations from cancer cells, glycolysis was reported to produce less entropy than mitochondrial oxidative phosphorylation. However, these estimations depended on the CO2 concentration so that at slightly increased CO2, it was oxidative phosphorylation that produced less entropy. Also, the thermodynamic efficiency of mitochondrial respiratory complexes varies depending on the respiratory state and oxidant/antioxidant balance. Therefore, in spite of long-standing theoretical and practical efforts, more measurements, also in isolated mitochondria, with intact and suboptimal respiration, are needed to resolve the issue. Entropy increases in ageing while mitochondrial efficiency of energy conversion, quality control, and turnover mechanisms deteriorate. Optimally functioning mitochondria are necessary to meet energy demands for cellular defence and repair processes to attenuate ageing. The intuitive approach of simply supplying more metabolic fuels (more nutrients) often has the opposite effect, namely a decrease in energy production in the case of nutrient overload. Excessive nutrient intake and obesity accelerate ageing, while calorie restriction without malnutrition can prolong life. Balanced nutrient intake adapted to needs/activity-based high ATP requirement increases mitochondrial respiratory efficiency and leads to multiple alterations in gene expression and metabolic adaptations. Therefore, rather than overfeeding, it is necessary to fine-tune energy production by optimizing mitochondrial function and reducing oxidative stress; the evidence is discussed in this paper.

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Non-equilibrium thermodynamics of biological signal transduction predicts conservation of entropy production rate

Cited by 10 publications

References 19 publications

Epidermal growth factor receptor cascade prioritizes the maximization of signal transduction

Epidermal growth factor receptor cascade prioritizes the maximization of signal transduction

Deriving the Fluctuation Theorem for Information-Transmission Systems Using a Cyclic Chain-Reaction Sequence

Decreasing Intracellular Entropy by Increasing Mitochondrial Efficiency and Reducing ROS Formation—The Effect on the Ageing Process and Age-Related Damage

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