Active Vertex Model for Cell-resolution Description of Epithelial Tissue Mechanics

Overview

Journal PLoS Comput Biol

Specialty Biology

Date 2017 Jul 1

PMID 28665934

Citations 56

Authors

Daniel L Barton

Silke Henkes

Cornelis J Weijer

Rastko Sknepnek

Affiliations

Soon will be listed here.

Abstract

We introduce an Active Vertex Model (AVM) for cell-resolution studies of the mechanics of confluent epithelial tissues consisting of tens of thousands of cells, with a level of detail inaccessible to similar methods. The AVM combines the Vertex Model for confluent epithelial tissues with active matter dynamics. This introduces a natural description of the cell motion and accounts for motion patterns observed on multiple scales. Furthermore, cell contacts are generated dynamically from positions of cell centres. This not only enables efficient numerical implementation, but provides a natural description of the T1 transition events responsible for local tissue rearrangements. The AVM also includes cell alignment, cell-specific mechanical properties, cell growth, division and apoptosis. In addition, the AVM introduces a flexible, dynamically changing boundary of the epithelial sheet allowing for studies of phenomena such as the fingering instability or wound healing. We illustrate these capabilities with a number of case studies.

Citing Articles

Cell-Level Modelling of Homeostasis in Confined Epithelial Monolayers.

Chaithanya K, Rozman J, Kosmrlj A, Sknepnek R J Elast. 2025; 157(2):29.

PMID: 40013236 PMC: 11850549. DOI: 10.1007/s10659-025-10120-0.

Inferring active and passive mechanical drivers of epithelial convergent extension.

Anjum S, Vijayraghavan D, Fernandez-Gonzalez R, Sutherland A, Davidson L bioRxiv. 2025; .

PMID: 39975291 PMC: 11838355. DOI: 10.1101/2025.01.28.635314.

Deciphering the interplay between biology and physics with a finite element method-implemented vertex organoid model: A tool for the mechanical analysis of cell behavior on a spherical organoid shell.

Laussu J, Michel D, Magne L, Segonds S, Marguet S, Hamel D PLoS Comput Biol. 2025; 21(1):e1012681.

PMID: 39792958 PMC: 11771887. DOI: 10.1371/journal.pcbi.1012681.

Vertex model with internal dissipation enables sustained flows.

Rozman J, Chaithanya K, Yeomans J, Sknepnek R Nat Commun. 2025; 16(1):530.

PMID: 39789022 PMC: 11718050. DOI: 10.1038/s41467-025-55820-2.

Initiation of epithelial wound closure by an active instability at the purse string.

Movrin V, Krajnc M Biophys J. 2024; 124(1):107-114.

PMID: 39543877 PMC: 11739890. DOI: 10.1016/j.bpj.2024.11.008.

References

Perrone M, Veldhuis J, Brodland G . Non-straight cell edges are important to invasion and engulfment as demonstrated by cell mechanics model. Biomech Model Mechanobiol. 2015; 15(2):405-18. PMC: 4792343. DOI: 10.1007/s10237-015-0697-6. View

Meineke F, Potten C, Loeffler M . Cell migration and organization in the intestinal crypt using a lattice-free model. Cell Prolif. 2001; 34(4):253-66. PMC: 6495866. DOI: 10.1046/j.0960-7722.2001.00216.x. View

Guillot C, Lecuit T . Mechanics of epithelial tissue homeostasis and morphogenesis. Science. 2013; 340(6137):1185-9. DOI: 10.1126/science.1235249. View

Ilina O, Friedl P . Mechanisms of collective cell migration at a glance. J Cell Sci. 2009; 122(Pt 18):3203-8. DOI: 10.1242/jcs.036525. View

Sanchez-Gutierrez D, Tozluoglu M, Barry J, Pascual A, Mao Y, Escudero L . Fundamental physical cellular constraints drive self-organization of tissues. EMBO J. 2015; 35(1):77-88. PMC: 4718000. DOI: 10.15252/embj.201592374. View

Deforet M, Hakim V, Yevick H, Duclos G, Silberzan P . Emergence of collective modes and tri-dimensional structures from epithelial confinement. Nat Commun. 2014; 5:3747. DOI: 10.1038/ncomms4747. View

Discher D, Janmey P, Wang Y . Tissue cells feel and respond to the stiffness of their substrate. Science. 2005; 310(5751):1139-43. DOI: 10.1126/science.1116995. View

Sandersius S, Chuai M, Weijer C, Newman T . Correlating cell behavior with tissue topology in embryonic epithelia. PLoS One. 2011; 6(4):e18081. PMC: 3084706. DOI: 10.1371/journal.pone.0018081. View

Collinet C, Rauzi M, Lenne P, Lecuit T . Local and tissue-scale forces drive oriented junction growth during tissue extension. Nat Cell Biol. 2015; 17(10):1247-58. DOI: 10.1038/ncb3226. View

10.

Harris A, Wild P, Stopak D . Silicone rubber substrata: a new wrinkle in the study of cell locomotion. Science. 1980; 208(4440):177-9. DOI: 10.1126/science.6987736. View

11.

Fletcher A, Osterfield M, Baker R, Shvartsman S . Vertex models of epithelial morphogenesis. Biophys J. 2014; 106(11):2291-304. PMC: 4052277. DOI: 10.1016/j.bpj.2013.11.4498. View

12.

Gibson M, Patel A, Nagpal R, Perrimon N . The emergence of geometric order in proliferating metazoan epithelia. Nature. 2006; 442(7106):1038-41. DOI: 10.1038/nature05014. View

13.

Bosveld F, Bonnet I, Guirao B, Tlili S, Wang Z, Petitalot A . Mechanical control of morphogenesis by Fat/Dachsous/Four-jointed planar cell polarity pathway. Science. 2012; 336(6082):724-7. DOI: 10.1126/science.1221071. View

14.

Etournay R, Popovic M, Merkel M, Nandi A, Blasse C, Aigouy B . Interplay of cell dynamics and epithelial tension during morphogenesis of the Drosophila pupal wing. Elife. 2015; 4:e07090. PMC: 4574473. DOI: 10.7554/eLife.07090. View

15.

Okuda S, Inoue Y, Eiraku M, Sasai Y, Adachi T . Modeling cell proliferation for simulating three-dimensional tissue morphogenesis based on a reversible network reconnection framework. Biomech Model Mechanobiol. 2012; 12(5):987-96. DOI: 10.1007/s10237-012-0458-8. View

16.

Poujade M, Grasland-Mongrain E, Hertzog A, Jouanneau J, Chavrier P, Ladoux B . Collective migration of an epithelial monolayer in response to a model wound. Proc Natl Acad Sci U S A. 2007; 104(41):15988-93. PMC: 2042149. DOI: 10.1073/pnas.0705062104. View

17.

Foty R, Steinberg M . The differential adhesion hypothesis: a direct evaluation. Dev Biol. 2005; 278(1):255-63. DOI: 10.1016/j.ydbio.2004.11.012. View

18.

Elosegui-Artola A, Bazellieres E, Allen M, Andreu I, Oria R, Sunyer R . Rigidity sensing and adaptation through regulation of integrin types. Nat Mater. 2014; 13(6):631-7. PMC: 4031069. DOI: 10.1038/nmat3960. View

19.

Zallen J . Planar polarity and tissue morphogenesis. Cell. 2007; 129(6):1051-63. DOI: 10.1016/j.cell.2007.05.050. View

20.

Osterfield M, Du X, Schupbach T, Wieschaus E, Shvartsman S . Three-dimensional epithelial morphogenesis in the developing Drosophila egg. Dev Cell. 2013; 24(4):400-10. PMC: 4080892. DOI: 10.1016/j.devcel.2013.01.017. View