The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
A theoretical basis for cell deaths
Open accessPreprint — published as 10.1103/physrevresearch.6.043217 · Paper page
Abstract
Understanding deaths and life-death boundaries of cells is a fundamental challenge in biological sciences. In this study, we present a theoretical framework for investigating cell death. We conceptualize cell death as a controllability problem within dynamical systems, and compute the life-death boundary through the development of “stoichiometric rays”. This method utilizes enzyme activity as control parameters, exploiting the inherent property of enzymes to enhance reaction rates without affecting thermodynamic potentials. This approach facilitates the efficient evaluation of the global controllability of models. We demonstrate the utility of our framework using its application to a toy metabolic model, where we delineate the life-death boundary. The formulation of cell death through mathematical principles provides a foundation for the theoretical study of cellular mortality. SIGNIFICANCE STATEMENT: What is death? This fundamental question in biology lacks a clear theoretical framework despite numerous experimental studies. In this study, we present a new way to understand cell death by looking at how cells can or cannot control their states. We define a “dead state” as a state from which a cell cannot return to being alive. Our method, called “Stoichiometric Rays”, helps determine if a cell’s state is dead based on enzymatic reactions. By using this method, we can quantify the life-death boundary in metabolic models. The present framework provides a theoretical basis and a tool for understanding cell death.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Deep learning-based kcat prediction enables improved enzyme-constrained model reconstruction
Li, F., Yuan, L., Lu, H., Li, G., Chen, Y., Engqvist, M. K. M., Kerkhoven, E. J., & Nielsen, J. (2022) · Nature Catalysis · doi:10.1038/s41929-022-00798-z · Cited by 466
Flagged first, then by citations
Research works printed but not linked: 53
- Antonio Casolari . Microbial death. In Physiological models in microbiology, pages 1–44. CRC press, 2018. · DOI
- 10.1371/journal.pbio.2001109 · DOI
- Eric C Spivey , Stephen K Jones, Jr , James R Rybarski , Fatema A Saifuddin , and Ilya J Finkelstein . An aging-independent replicative lifespan in a symmetrically dividing eukaryote. Elife, 6, January 2017. · DOI
- 10.1016/j.cub.2010.04.045 · DOI · Paper page
- 10.1038/cddis.2014.570 · DOI
- 10.1128/AEM.01527-09 · DOI
- 10.1016/j.jtbi.2011.10.007 · DOI
- Y Himeoka and N Mitarai . Dynamics of bacterial populations under the feast-famine cycles. Physical Review Research, 2020. · DOI
- 2019, Death rate of e. coli during starvation is set by maintenance cost and biomass recycling, Cell Syst, 9, 64, 10.1016/j.cels.2019.06.003 · DOI
- 10.15252/msb.20209478 · DOI
- 10.15252/msb.20199245 · DOI
- 2024, Bacterial killing and the dimensions of bacterial death, NPJ Biofilms Microbiomes, 10, 87, 10.1038/s41522-024-00559-9 · DOI
- SJ Schink , M Polk , E Athaide , A Mukherjee , C Ammar , and others. The energy requirements of ion homeostasis determine the lifespan of starving bacteria. bioRxiv, 2021. · DOI
- 10.1038/s41467-019-09078-0 · DOI
- M Umetani , M Fujisawa , R Okura , T Nozoe , S Suenaga , H Nakaoka , E Kussell , and Y Wakamoto . Observation of non-dormant persister cells reveals diverse modes of survival in antibiotic persistence. 2021. · DOI
- 2022, Slowest possible replicative life at frigid temperatures for yeast, Nat. Commun, 13, 7518, 10.1038/s41467-022-35151-2 · DOI
- Rachel M Walker , Valeria C Sanabria , and Hyun Youk . Microbial life in slow and stopped lanes. Trends Microbiol., December 2023. · DOI
- 10.1111/j.1574-6976.2009.00200.x · DOI
- 10.1007/BF02010671 · DOI
- 2021, ‘viable but non-culturable cells’ are dead, Environ. Microbiol, 23, 2335, 10.1111/1462-2920.15463 · DOI
- Alexander K T Kirschner , Julia Vierheilig , Hans-Curt Flemming, Jost Wingender, and An-dreas H Farnleitner. How dead is dead? viable but non-culturable versus persister cells. Environ. Microbiol. Rep., 13(3), 2021. · DOI
- 10.1007/s12275-019-9218-0 · DOI
- 10.3389/fmicb.2014.00070 · DOI
- 10.1016/j.gde.2011.10.001 · DOI · Paper page
- 10.1126/science.1099390 · DOI · Paper page
- 10.1038/s41579-019-0207-4 · DOI
- 10.1038/43199 · DOI · Paper page
- HC Berg . Rotary motor. In Howard C Berg , editor, E. coli in Motion, pages 105–120. Springer New York, New York, NY, 2004.
- 10.1073/pnas.0706792104 · DOI
- 10.1126/science.1183372 · DOI
- 10.1073/pnas.71.10.4135 · DOI · Paper page
- 10.1016/j.cell.2021.12.025 · DOI · Paper page
- 2022, Reconstructing kinetic models for dynamical studies of metabolism using generative adversarial networks, Nat Mach Intell, 4, 710, 10.1038/s42256-022-00519-y · DOI
- Y Himeoka and N Mitarai . Emergence of growth and dormancy from a kinetic model of the escherichia coli central carbon metabolism. Physical Review Research, 2022. · DOI
- Jacqueline I Stone and Mariko Namba Walter . Death and the afterlife in Japanese Buddhism. University of Hawaii Press, 2008.
- 10.1021/ar000058i · DOI
- 1973, Global controllability of linear systems with positive controls, SIAM J. Control Optim, 11, 417, 10.1137/0311034 · DOI
- 1998, Local controllability of reactions, J. Math. Chem, 24, 1
- 1992, Local observability and controllability of stirred tank reactors, J. Process Control, 2, 139, 10.1016/0959-1524(92)85003-F · DOI
- 2016, Global controllability of chemical reactions, J. Math. Chem, 54, 1327, 10.1007/s10910-016-0626-7 · DOI
- Peter William Atkins , Julio De Paula , and James Keeler . Atkins’ physical chemistry. Oxford university press, 2023.
- Martin Feinberg . Foundations of Chemical Reaction Network Theory. Springer, Cham, 2019. · DOI
- A. Cornish-Bowden . Fundamentals of Enzyme Kinetics. Wiley, 2013. · DOI
- Henk Nijmeijer and Arjan Van der Schaft . Nonlinear dynamical control systems, volume 464. Springer, 1990. · DOI
- 2004, Transmissible spongiform en-cephalopathies, The Lancet, 363, 51, 10.1016/S0140-6736(03)15171-9 · DOI
- Erwin Schrödinger . What is life? The physical aspect of the living cell and mind. Cambridge university press Cambridge, 1944.
- 10.1098/rspb.1965.0069 · DOI
- 10.1016/j.ygyno.2016.05.032 · DOI
- 10.1371/journal.pbio.3001586 · DOI
- 10.1002/cbin.11137 · DOI
- 10.1016/j.cell.2023.11.044 · DOI
- 2024, A guide to cell death pathways, Nat. Rev. Mol. Cell Biol, 25, 379, 10.1038/s41580-023-00689-6 · DOI
- 2023, Diversity and complexity of cell death: a historical review, Exp. Mol. Med, 55, 1573, 10.1038/s12276-023-01078-x · DOI
Metadata
- Authors
- Himeoka, Y., Horiguchi, S. A., & Kobayashi, T. J.
- Affiliations
- Universal Biology Institute, The University of Tokyo (JP)
- Kanazawa University (JP)
- Institute of Industrial Science, The University of Tokyo (JP)
- Corresponding author
- Himeoka, Yusuke
- Venue
- Physical Review Research
- Publisher
- openRxiv
- Published
- 2024-03-08
- Volume
- 6
- Issue
- 4
- ISSN
- 2643-1564 (ISSN-L)
- OpenAlex
- W4404757745
- Cited by
- 5
- References
- 1
- Citations by year
- 2026: 3 · 2025: 2
- FWCI
- 0.68
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Physical Review Research (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- arXiv (Cornell University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- arXiv (Cornell University) (cc-by)
- Funders
- Japan Society for the Promotion of Science (JP21J21415, 22K15069, 24H01118, JPMJGX23B4, JP22H05403, 24K00542, 24KJ0090, JP24H01118, JPMJCR2011, 19H05799)
- Japan Science and Technology Agency (JPMJCR2011, JPMJGX23B4, JPMJCR1927)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Physical Sciences › Mathematics › Modeling and Simulation › Mathematical Biology Tumor Growth
- Keywords
- cell death, controllability, dynamical systems, enzyme activity, metabolic modeling, global controllability, thermodynamic potential
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
