Monitoring and modeling of lymphocytic leukemia cell bioenergetics reveals decreased ATP synthesis during cell division DOI Creative Commons
Joon Ho Kang, Georgios Katsikis,

Zhaoqi Li

et al.

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Oct. 5, 2020

Abstract The energetic demands of a cell are believed to increase during mitosis, but the rates ATP synthesis and consumption mitosis have not been quantified. Here, we monitor mitochondrial membrane potential single lymphocytic leukemia cells demonstrate that mitochondria hyperpolarize from G2/M transition until metaphase-anaphase transition. This hyperpolarization was dependent on cyclin-dependent kinase 1 (CDK1) activity. By using an electrical circuit model mitochondria, quantify in single-cell time-dynamics potential. We find decreases by approximately 50% early increases back G2 levels cytokinesis. Consistently, lower than synchronized populations. Overall, our results provide insights into mitotic bioenergetics suggest division is highly energy demanding process.

Language: Английский

Geometry of Optimal Control in Chemical Reaction Networks in the Adiabatic Limit DOI

Yikuan Zhang,

Qi Ouyang, Yuhai Tu

et al.

Physical Review Letters, Journal Year: 2025, Volume and Issue: 134(1)

Published: Jan. 6, 2025

Although optimal control (OC) has been studied in stochastic thermodynamics for systems with continuous state variables, less is known discrete such as chemical reaction networks (CRNs). Here, we develop a general theoretical framework to study OC of CRNs changing the system from an initial distribution states final minimum dissipation. We derive "Kirchhoff's law" probability current adiabatic limit, which kinetic rates are determined analytically any given trajectory allowed by local rate constraints. By using rates, show that total dissipation L_{2}-distance measure space and analytical expression metric tensor depends on distribution, network topology, capacity each link. Minimizing leads geodesic corresponding protocol Kirchhoff's law. To demonstrate our approach, use it find lower bound tighter than existing bounds obtained only global constraints limit. also apply simple networks, e.g., fully connected three-state different indirect pathway nonfunctional transient can play crucial role switching between distributions efficiently. Future directions studying discussed.

Language: Английский

Citations

2
Physical bioenergetics: Energy fluxes, budgets, and constraints in cells DOI Open Access
Xingbo Yang, Matthias Heinemann, Jonathon Howard

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(26)

Published: June 17, 2021

Cells are the basic units of all living matter which harness flow energy to drive processes life. While biochemical networks involved in transduction well-characterized, energetic costs and constraints for specific cellular remain largely unknown. In particular, what budgets cells? What limits flows impose on processes? Do cells operate near these limits, if so how do impact functions? Physics has provided many tools study nonequilibrium systems define physical but applying cell biology remains a challenge. Physical bioenergetics, resides at interface physics, metabolism, biology, seeks understand much using, they partition this between different processes, associated constraints. Here we review recent advances discuss open questions challenges bioenergetics.

Language: Английский

Citations

101
Improved bounds on entropy production in living systems DOI Open Access
Dominic J. Skinner, Jörn Dunkel

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(18)

Published: April 27, 2021

Significance Thermodynamic laws fundamentally limit the efficiency and accuracy of living systems. To perform essential functions, from sensing to replication locomotion, organisms consume energy dissipate heat. The rate at which they can be bounded, in theory, by measuring all their internal variables. In practice, however, entire system is rarely experimentally observable, many states remain hidden. Here, we introduce a mathematical framework that yields optimal bounds on consumption when only small number observables are available. Overcoming previous limitations, our approach discovers nonzero even observed trajectories time symmetric. We demonstrate practical usefulness this method applications variety recent experimental data.

Language: Английский

Citations

93
Theoretical perspectives on biological machines DOI Creative Commons
Mauro L. Mugnai, Changbong Hyeon, Michael Hinczewski

et al.

Reviews of Modern Physics, Journal Year: 2020, Volume and Issue: 92(2)

Published: April 7, 2020

By operating out of equilibrium, nanoscale biological machines execute many functions that do not take place in abiotic systems. Statistical physics, physical chemistry, and polymer physics principles are needed elucidating the rules constraints governing large-scale structural changes occur when metabolizing molecular fuel. This paper reviews advances theories rooted coarse graining complex systems while reminding us details must be an integral part a deeper understanding processes living

Language: Английский

Citations

77
Gene Regulation and Cellular Metabolism: An Essential Partnership DOI Creative Commons
Richard W. Carthew

Trends in Genetics, Journal Year: 2020, Volume and Issue: 37(4), P. 389 - 400

Published: Oct. 19, 2020

Language: Английский

Citations

76
Glycolytic flux-signaling controls mouse embryo mesoderm development DOI Creative Commons
Hidenobu Miyazawa, Marteinn T. Snaebjornsson, Nicole Prior

et al.

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Dec. 5, 2022

How cellular metabolic state impacts programs is a fundamental, unresolved question. Here, we investigated how glycolytic flux embryonic development, using presomitic mesoderm (PSM) patterning as the experimental model. First, identified fructose 1,6-bisphosphate (FBP) an in vivo sentinel metabolite that mirrors within PSM cells of post-implantation mouse embryos. We found medium-supplementation with FBP, but not other metabolites, such 6-phosphate and 3-phosphoglycerate, impaired segmentation. To genetically manipulate FBP levels, generated model enabling conditional overexpression dominant active, cytoplasmic PFKFB3 (cytoPFKFB3). Overexpression cytoPFKFB3 indeed led to increased flux/FBP levels caused impairment segmentation, paralleled by downregulation Wnt-signaling, reminiscent effects seen upon FBP-supplementation. probe for mechanisms underlying flux-signaling, performed subcellular proteome analysis revealed altered localization certain proteins, including enzymes, cells. Specifically, supplementation depletion Pfkl Aldoa from nuclear-soluble fraction. Combined, propose functions flux-signaling connecting glycolysis patterning, potentially through modulating protein localization.

Language: Английский

Citations

35
Polyploidy in Xenopus lowers metabolic rate by decreasing total cell surface area DOI Creative Commons
Clotilde Cadart, Julianne Bartz,

Gillian Oaks

et al.

Current Biology, Journal Year: 2023, Volume and Issue: 33(9), P. 1744 - 1752.e7

Published: April 19, 2023

Although polyploidization is frequent in development, cancer, and evolution, impacts on animal metabolism are poorly understood. In Xenopus frogs, the number of genome copies (ploidy) varies across species can be manipulated within a species. Here, we show that triploid tadpoles contain fewer, larger cells than diploids consume oxygen at lower rate. Drug treatments revealed major processes accounting for tadpole energy expenditure include cell proliferation, biosynthesis, maintenance plasma membrane potential. While inhibiting proliferation did not abolish consumption difference between triploids, altered cellular biosynthesis or electrical potential did. Combining these results with simple mathematical framework, propose decrease total surface area lowered production activity components including Na

Language: Английский

Citations

18
Lessons from equilibrium statistical physics regarding the assembly of protein complexes DOI Creative Commons
Pablo Sartori, Stanislas Leibler

Proceedings of the National Academy of Sciences, Journal Year: 2019, Volume and Issue: 117(1), P. 114 - 120

Published: Dec. 23, 2019

Significance In order to carry out their functions, most proteins assemble into multicomponent complexes. the process of assembly, complexes need discriminate specific components from a mixture hundreds different present in cell. To assess some implications this requirement, we develop minimal model self-assembly based on equilibrium statistical physics. We argue that reliably imposes fundamental constraints characteristics complexes, which support with analysis available structural and compositional data. Our work constitutes only step toward future theory protein complex will have incorporate also nonequilibrium kinetic aspects rich, yet theoretically neglected, problem.

Language: Английский

Citations

48
A Theoretical Framework for Evolutionary Cell Biology DOI Creative Commons
Michael Lynch, Bogi Trickovic

Journal of Molecular Biology, Journal Year: 2020, Volume and Issue: 432(7), P. 1861 - 1879

Published: Feb. 19, 2020

Language: Английский

Citations

43
Fractal Pennes and Cattaneo–Vernotte bioheat equations from product-like fractal geometry and their implications on cells in the presence of tumour growth DOI Open Access
Rami Ahmad El‐Nabulsi

Journal of The Royal Society Interface, Journal Year: 2021, Volume and Issue: 18(182), P. 20210564 - 20210564

Published: Sept. 1, 2021

In this study, the Pennes and Cattaneo-Vernotte bioheat transfer equations in presence of fractal spatial dimensions are derived based on product-like geometry. This approach was introduced recently, by Li Ostoja-Starzewski, order to explore dynamical properties anisotropic media. The theory is characterized a modified gradient operator which depends two parameters: R represents radius tumour R0 spherical living tissue. Both steady unsteady states for each equation were obtained their implications cells growth large analysed. Assuming specific heating/cooling constant heat flux equivalent metabolic generation tissue, it observed that solutions robustly affected dimensions, cell ranges both temperature obtained, analysed compared with recent studies. study confirms importance fractals medicine.

Language: Английский

Citations

39