Academic Journal
Cooperation, Defection, and Collapse: A Multiscale Game Theory Framework for Emphysema Progression.
| Τίτλος: | Cooperation, Defection, and Collapse: A Multiscale Game Theory Framework for Emphysema Progression. |
|---|---|
| Συγγραφείς: | Cantor J; School of Pharmacy and Applied Health Sciences, St John's University, Queens, NY 11439, USA. |
| Πηγή: | Cells [Cells] 2026 Aug 17; Vol. 15 (16). Date of Electronic Publication: 2026 Aug 17. |
| Τύπος έκδοσης: | Journal Article; Review |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Basel, Switzerland : MDPI |
| Ιατρικοί όροι (MeSH): | Pulmonary Emphysema*/pathology , Pulmonary Emphysema*/physiopathology , Pulmonary Emphysema*/metabolism , Game Theory* , Disease Progression*, Extracellular Matrix/metabolism ; Collagen/metabolism ; Humans ; Models, Biological ; Animals |
| Περίληψη: | In the current paper, pulmonary emphysema is hypothesized to emerge from a nonlinear breakdown of cooperation across two tightly coupled systems: the extracellular matrix (ECM) crosslink network and the cellular populations responsible for its maintenance. To formalize this concept, we construct a game-theoretic model that unifies the mechanical failure, inflammatory changes, and percolation-driven tissue collapse that are recognized features of the disease. At the ECM level, elastin and collagen crosslinks are modeled as players in an iterated Prisoner's Dilemma, where cooperation corresponds to maintaining structural integrity, and defection corresponds to rupture under mechanical stress. At the cellular level, fibroblasts, macrophages, and neutrophils engage in a parallel strategic game in which repair reflects cooperative activity, and protease- or oxidant-producing phenotypes are indicative of defection. These parallel games are coupled through bidirectional payoff modulation, generating a dynamical system with bistability, tipping points, and runaway positive feedback. As the fraction of intact crosslinks falls below a critical percolation threshold, global network connectivity collapses and lung function drops precipitously. This framework explains the characteristic features of pulmonary emphysema, including spatial heterogeneity, abrupt acceleration, and irreversibility as emergent properties of coupled cooperation-defection dynamics, and identifies new leverage points for stabilizing cooperation and preventing catastrophic network failure in early disease. In support of this hypothesis, we present previously published studies from our laboratory involving measurements of elastin-specific desmosine crosslinks in human postmortem emphysematous lungs showing a marked increase in tissue crosslink density at the early stage of the disease, and accelerating loss of these crosslinks as airspace enlargement progresses, consistent with initial cooperation followed by defection. This conceptual framework is then applied to the poorly understood lung disease, Combined Pulmonary Fibrosis and Emphysema, to provide a potential mechanism for its pathogenesis. |
| References: | Biomolecules. 2023 Mar 22;13(3):. (PMID: 36979509) Biomed Mater. 2021 Oct 19;16(6):. (PMID: 34587604) FEBS J. 2024 Feb;291(3):430-440. (PMID: 37612040) Int J Mol Sci. 2025 Oct 30;26(21):. (PMID: 41226611) Proc Natl Acad Sci U S A. 2017 Jun 6;114(23):6046-6051. (PMID: 28533405) Am J Epidemiol. 2023 Oct 10;192(10):1647-1658. (PMID: 37160347) Front Immunol. 2026 May 08;17:1709410. (PMID: 42183253) Eur Respir J. 2024 Oct 31;64(4):. (PMID: 39209469) Int J Chron Obstruct Pulmon Dis. 2020 Aug 06;15:1909-1918. (PMID: 32821093) Cells. 2024 Mar 02;13(5):. (PMID: 38474402) Essays Biochem. 2020 Sep 23;64(3):443-462. (PMID: 32885825) Lancet. 2017 May 13;389(10082):1931-1940. (PMID: 28513453) Cell Biosci. 2022 Jul 27;12(1):117. (PMID: 35897082) Expert Rev Mol Diagn. 2021 Oct;21(10):1049-1064. (PMID: 34330194) Nat Rev Immunol. 2026 Jun;26(6):455-471. (PMID: 41680464) Cells. 2021 Aug 20;10(8):. (PMID: 34440917) Am J Cancer Res. 2023 Sep 15;13(9):4478-4489. (PMID: 37818082) Ann Am Thorac Soc. 2018 Dec;15(Suppl 4):S227-S233. (PMID: 30759011) Sci Rep. 2021 Aug 17;11(1):16654. (PMID: 34404841) Matrix Biol. 1998 Feb;16(7):387-98. (PMID: 9524359) Nat Commun. 2025 Nov 26;16(1):11655. (PMID: 41298466) J Clin Med. 2020 May 11;9(5):. (PMID: 32403382) Chest. 2013 Jul;144(1):266-273. (PMID: 23880677) Eur Respir J. 2005 Oct;26(4):586-93. (PMID: 16204587) Am J Respir Crit Care Med. 2020 Feb 1;201(3):294-302. (PMID: 31657634) Expert Rev Respir Med. 2024 Jun;18(6):349-354. (PMID: 38949832) Int J Environ Res Public Health. 2011 Jan;8(1):161-84. (PMID: 21318022) Biomedicines. 2025 Aug 30;13(9):. (PMID: 41007683) Front Immunol. 2022 Jul 08;13:928134. (PMID: 35880175) Eur J Med Res. 2023 Mar 20;28(1):127. (PMID: 36935521) Int J Mol Sci. 2023 Feb 14;24(4):. (PMID: 36835197) Chronic Obstr Pulm Dis. 2021 Apr 27;8(2):198-212. (PMID: 33290645) J Allergy Clin Immunol. 2016 Jul;138(1):16-27. (PMID: 27373322) J Pathol. 2020 Apr;250(5):624-635. (PMID: 31691283) Crit Rev Biochem Mol Biol. 2020 Jun;55(3):252-273. (PMID: 32530323) J Appl Physiol (1985). 2011 Apr;110(4):1111-8. (PMID: 21212247) Nat Genet. 2026 Feb;58(2):376-391. (PMID: 41578022) Immunity. 2021 May 11;54(5):903-915. (PMID: 33979587) NPJ Digit Med. 2025 Aug 28;8(1):556. (PMID: 40877584) Dyn Games Appl. 2022;12(1):7-48. (PMID: 35194521) Proc Natl Acad Sci U S A. 2020 Apr 14;117(15):8326-8334. (PMID: 32238564) Expert Rev Respir Med. 2025 Feb 25;:1-12. (PMID: 39912527) Biomedicines. 2025 Dec 26;14(1):. (PMID: 41595593) Cells. 2025 May 12;14(10):. (PMID: 40422205) Biomolecules. 2023 Jun 06;13(6):. (PMID: 37371525) Eur Respir Rev. 2020 Nov 18;29(158):. (PMID: 33208482) Thorax. 2016 Feb;71(2):126-32. (PMID: 26645414) Math Biosci. 2023 Nov;365:109074. (PMID: 37689347) Nat Commun. 2020 Feb 14;11(1):915. (PMID: 32060275) Antioxidants (Basel). 2023 Feb 21;12(3):. (PMID: 36978796) J Mech Behav Biomed Mater. 2015 Dec;52:1-13. (PMID: 25153614) Am J Respir Crit Care Med. 2022 Aug 15;206(4):e7-e41. (PMID: 35969190) Chest. 2022 Mar;161(3):651-661. (PMID: 34592319) Am J Respir Crit Care Med. 2023 Apr 1;207(7):819-837. (PMID: 36856433) Antioxidants (Basel). 2022 Feb 26;11(3):. (PMID: 35326114) COPD. 2025 Jul;22(1):2525433. (PMID: 40620021) Cell Commun Signal. 2024 Mar 9;22(1):172. (PMID: 38461312) Biomater Adv. 2025 Jul;172:214240. (PMID: 40023083) Front Med (Lausanne). 2022 Jan 03;8:762878. (PMID: 35047522) Eur Respir Rev. 2023 Dec 20;32(170):. (PMID: 38123230) Immunol Rev. 2021 Jul;302(1):86-103. (PMID: 34101202) Int J Mol Sci. 2021 Dec 31;23(1):. (PMID: 35008850) Chest. 2019 Jan;155(1):79-87. (PMID: 30292758) Biomedicines. 2026 Jan 27;14(2):. (PMID: 41751180) FEBS J. 2026 Jul;293(13):3788-3813. (PMID: 41178498) Respirology. 2021 Apr;26(4):298-321. (PMID: 33506971) Macromolecules. 2018 Sep 11;51(17):6609-6622. (PMID: 31543548) Int J Mol Sci. 2024 May 22;25(11):. (PMID: 38891820) J R Soc Interface. 2022 Aug;19(193):20220346. (PMID: 35975562) J Bacteriol. 2017 Aug 28;199(22):. (PMID: 28847922) Front Bioeng Biotechnol. 2020 Dec 22;8:609653. (PMID: 33425874) Compr Physiol. 2022 Jun 29;12(3):3523-3558. (PMID: 35766837) Int J Mol Sci. 2017 Sep 09;18(9):. (PMID: 28891938) Essays Biochem. 2019 Sep 13;63(3):349-364. (PMID: 31488698) Nat Commun. 2018 Apr 10;9(1):1359. (PMID: 29636480) Eur Respir J. 2017 Jul 5;50(1):. (PMID: 28679607) Am J Respir Crit Care Med. 2007 Sep 15;176(6):617-23. (PMID: 17575096) Entropy (Basel). 2022 Jun 13;24(6):. (PMID: 35741542) Eur Respir Rev. 2022 Mar 9;31(163):. (PMID: 35264410) Int J Mol Sci. 2021 Aug 19;22(16):. (PMID: 34445658) J Mech Behav Biomed Mater. 2020 Oct;110:103849. (PMID: 32501220) J Immunol Res. 2021 Jul 16;2021:8243378. (PMID: 34327245) Ther Adv Respir Dis. 2022 Jan-Dec;16:17534666211070139. (PMID: 35156488) Adv Healthc Mater. 2020 Apr;9(8):e1901445. (PMID: 32037719) Am J Respir Crit Care Med. 2012 Jan 1;185(1):44-52. (PMID: 22016444) J R Soc Interface. 2023 Jul;20(204):20230301. (PMID: 37464799) Int J Mol Sci. 2024 Oct 02;25(19):. (PMID: 39408941) Tuberc Respir Dis (Seoul). 2023 Apr;86(2):71-81. (PMID: 37005090) Physiol Rev. 2022 Oct 1;102(4):1703-1720. (PMID: 35532056) Phys Rev E. 2020 Oct;102(4-1):042403. (PMID: 33212590) Biochem Soc Trans. 2024 Jun 26;52(3):1199-1217. (PMID: 38778764) Mol Biol Rep. 2023 Jan;50(1):339-348. (PMID: 36331745) Int J Chron Obstruct Pulmon Dis. 2021 Jan 28;16:167-177. (PMID: 33536752) Radiology. 2026 Mar;318(3):e260403. (PMID: 41914871) Medicina (Kaunas). 2019 Sep 10;55(9):. (PMID: 31509942) Nature. 2005 Oct 27;437(7063):1291-8. (PMID: 16251955) Chest. 2009 Jul;136(1):10-15. (PMID: 19225068) Respir Res. 2024 Feb 28;25(1):106. (PMID: 38419014) Cells. 2021 Feb 18;10(2):. (PMID: 33670759) Sci Rep. 2023 Jun 5;13(1):9125. (PMID: 37277442) Mayo Clin Proc. 2023 Nov;98(11):1685-1696. (PMID: 37923525) Thorax. 2020 Sep;75(9):744-753. (PMID: 32532852) Matrix Biol. 2020 Sep;91-92:1-7. (PMID: 32504772) Am J Physiol Lung Cell Mol Physiol. 2023 Jun 1;324(6):L747-L755. (PMID: 37014816) Pulmonology. 2025 Dec 31;31(1):2486881. (PMID: 40353713) Int J Mol Sci. 2024 Nov 02;25(21):. (PMID: 39519344) Am J Physiol Lung Cell Mol Physiol. 2026 Jun 01;330(6):L653-L660. (PMID: 42030197) Respir Res. 2019 Nov 12;20(1):254. (PMID: 31718676) Front Pharmacol. 2022 Jan 19;12:797292. (PMID: 35126134) |
| Contributed Indexing: | Keywords: combined pulmonary fibrosis and emphysema; extracellular matrix crosslinking; game theory; percolation theory; pulmonary emphysema |
| Substance Nomenclature: | 9007-34-5 (Collagen) |
| Entry Date(s): | Date Created: 20260826 Date Completed: 20260826 Latest Revision: 20260828 |
| Update Code: | 20260828 |
| PubMed Central ID: | PMC13510718 |
| DOI: | 10.3390/cells15161470 |
| PMID: | 42645198 |
| Βάση Δεδομένων: | MEDLINE |
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