Rigidity percolation uncovers a structural basis for embryonic tissue phase transitions
Open accessAbstract
Embryo morphogenesis is impacted by dynamic changes in tissue material properties, which have been proposed to occur via processes akin to phase transitions (PTs). Here, we show that rigidity percolation provides a simple and robust theoretical framework to predict material/structural PTs of embryonic tissues from local cell connectivity. By using percolation theory, combined with directly monitoring dynamic changes in tissue rheology and cell contact mechanics, we demonstrate that the zebrafish blastoderm undergoes a genuine rigidity PT, brought about by a small reduction in adhesion-dependent cell connectivity below a critical value. We quantitatively predict and experimentally verify hallmarks of PTs, including power-law exponents and associated discontinuities of macroscopic observables. Finally, we show that this uniform PT depends on blastoderm cells undergoing meta-synchronous divisions causing random and, consequently, uniform changes in cell connectivity. Collectively, our theoretical and experimental findings reveal the structural basis of material PTs in an organismal context.
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Embryonic tissue in its early stages lies close to the fluidization critical point, enabling the tissue to melt and thus induce a strong deformation to solidify again, to fix morphogenetic changes.
“For example, it has been reported that the embryonic tissue in its early stages lies close to the fluidization critical point, enabling the tissue to melt and thus induce a strong deformation to solidify again, to fix the morphogenetic changes [406].”
From Fundamental constraints to the logic of living systems (2024) · cites this paper as [406]
The Results sections on zebrafish blastoderm fluidization and rigidity percolation report a transition near a critical connectivity threshold: the blastoderm briefly fluidizes at the onset of morphogenesis, then regains viscosity and rigidity. The paper does not establish that this sequence enables strong deformation or fixes morphogenetic changes, and its findings concern the central zebrafish blastoderm rather than embryonic tissue generally. The indexed passages provide section labels but no page numbers. (LLM, conf=0.84)
Experimental — accuracy not yet measuredHuge fluctuations due to proximity to the critical point may represent a serious drawback for the precision of tissue development.
“In addition, huge fluctuations due to the proximity to the critical point may represent a serious drawback for the precision of tissue development [406].”
From Fundamental constraints to the logic of living systems (2024) · cites this paper as [406]
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Fiji: an open-source platform for biological-image analysis
Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S., Schmid, B., et al. (2012) · Nature Methods · doi:10.1038/nmeth.2019 · Cited by 66,890 · see citing works
Elements of Information Theory
Cover, T. M., & Thomas, J. A. (2005) · doi:10.1002/047174882x · Cited by 13,791 · see citing works
Silberblick/Wnt11 mediates convergent extension movements during zebrafish gastrulation
Heisenberg, C.-P., Tada, M., Rauch, G.-J., Saúde, L., Concha, M. L., Geisler, R., Stemple, D. L., Smith, J. C., & Wilson, S. W. (2000) · Nature · doi:10.1038/35011068 · Cited by 1,013 · see citing works
Self-citationA density-independent rigidity transition in biological tissues
Bi, D., Lopez, J. H., Schwarz, J. M., & Manning, M. L. (2015) · Nature Physics · doi:10.1038/nphys3471 · Cited by 801 · see citing works
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Research works printed but not linked: 75
- Alt S. Ganguly P. Salbreux G. Vertex models: from cell mechanics to tissue morphogenesis Philos. Trans. R. Soc. Lond. B Biol. Sci. 372 2017 20150520 28348254 PMC5379026
- Angelini T.E. Hannezo E. Trepat X. Marquez M. Fredberg J.J. Weitz D.A. Glass-like dynamics of collective cell migration Proc. Natl. Acad. Sci. USA 108 2011 4714 4719 21321233 PMC3064326
- Atia L. Bi D. Sharma Y. Mitchel J.A. Gweon B.A. Koehler S. DeCamp S.J. Lan B. Kim J.H. Hirsch R. Geometric constraints during epithelial jamming Nat. Physiol. 14 2018 613 620 PMC6108541 30151030
- Babb S.G. Marrs J.A. E-cadherin regulates cell movements and tissue formation in early zebrafish embryos Dev. Dyn. 230 2004 263 277 15162505
- Bardet P.-L. Guirao B. Paoletti C. Serman F. Léopold V. Bosveld F. Goya Y. Mirouse V. Graner F. Bellaïche Y. PTEN controls junction lengthening and stability during cell rearrangement in epithelial tissue Dev. Cell 25 2013 534 546 23707736
- Barone V. Lang M. Krens S.F.G. Pradhan S.J. Shamipour S. Sako K. Sikora M. Guet C.C. Heisenberg C.-P. An Effective Feedback Loop between Cell-Cell Contact Duration and Morphogen Signaling Determines Cell Fate Dev. Cell 43 2017 198 211.e12 29033362
- Barriga E.H. Franze K. Charras G. Mayor R. Tissue stiffening coordinates morphogenesis by triggering collective cell migration in vivo Nature 554 2018 523 527 29443958 PMC6013044
- Basan M. Elgeti J. Hannezo E. Rappel W.-J. Levine H. Alignment of cellular motility forces with tissue flow as a mechanism for efficient wound healing Proc. Natl. Acad. Sci. USA 110 2013 2452 2459 23345440 PMC3574962
- Bi D. Yang X. Marchetti M.C. Manning M.L. Motility-driven glass and jamming transitions in biological tissues Phys. Rev. X 6 2016 1 13 PMC5619672 28966874
- Bollobas B. Modern Graph Theory 1998 Springer US
- Brière M.A. Chubynsky M.V. Mousseau N. Self-organized criticality in the intermediate phase of rigidity percolation Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 75 2007 056108 17677134
- Cavanaugh K.E. Staddon M.F. Banerjee S. Gardel M.L. Adaptive viscoelasticity of epithelial cell junctions: from models to methods Curr. Opin. Genet. Dev. 63 2020 86 94 32604032 PMC7483996
- Chubynsky M.V. Thorpe M.F. Algorithms for three-dimensional rigidity analysis and a first-order percolation transition Phys. Rev. E Stat. Nonlin. Soft Matter Physiol. 76 2007 1 28 17994964
- David R. Luu O. Damm E.W. Wen J.W.H. Nagel M. Winklbauer R. Tissue cohesion and the mechanics of cell rearrangement Development 141 2014 3672 3682 25249459
- Detrich H.W. 3rd Westerfield M. Zon L.I. Overview of the Zebrafish system Methods Cell Biol. 59 1999 3 10 9891351
- Domb C. Green M.S. Phase transitions and critical phenomena 1972 Academic Press
- Douezan S. Guevorkian K. Naouar R. Dufour S. Cuvelier D. Brochard-Wyart F. Spreading dynamics and wetting transition of cellular aggregates Proc. Natl. Acad. Sci. USA 108 2011 7315 7320 21504944 PMC3088609
- Farhadifar R. Röper J.-C. Aigouy B. Eaton S. Jülicher F. The influence of cell mechanics, cell-cell interactions, and proliferation on epithelial packing Curr. Biol. 17 2007 2095 2104 18082406
- Firmino J. Rocancourt D. Saadaoui M. Moreau C. Gros J. Cell Division Drives Epithelial Cell Rearrangements during Gastrulation in Chick Dev. Cell 36 2016 249 261 26859350 PMC6485541
- Fletcher A.G. Osterfield M. Baker R.E. Shvartsman S.Y. Vertex models of epithelial morphogenesis Biophys. J. 106 2014 2291 2304 24896108 PMC4052277
- Forgacs G. Foty R.A. Shafrir Y. Steinberg M.S. Viscoelastic properties of living embryonic tissues: a quantitative study Biophys. J. 74 1998 2227 2234 9591650 PMC1299566
- Garcia S. Hannezo E. Elgeti J. Joanny J.-F. Silberzan P. Gov N.S. Physics of active jamming during collective cellular motion in a monolayer Proc. Natl. Acad. Sci. USA 112 2015 15314 15319 26627719 PMC4687586
- Gonzalez-Rodriguez D. Guevorkian K. Douezan S. Brochard-Wyart F. Soft Matter Models of Developing Tissues and Tumors Science 338 2012 910 917 23161991
- Guevorkian K. Colbert M.J. Durth M. Dufour S. Brochard-Wyart F. Aspiration of biological viscoelastic drops Phys. Rev. Lett. 104 2010 218101 20867138
- Haeger A. Krause M. Wolf K. Friedl P. Cell jamming: collective invasion of mesenchymal tumor cells imposed by tissue confinement Biochim. Biophys. Acta 1840 2014 2386 2395 24721714
- Hanel R. Corominas-Murtra B. Liu B. Thurner S. Fitting power-laws in empirical data with estimators that work for all exponents PLoS ONE 12 2017 e0170920 28245249 PMC5330461
- Hannezo E. Heisenberg C.P. Mechanochemical Feedback Loops in Development and Disease Cell 178 2019 12 25 31251912
- Heisenberg C.P. Bellaïche Y. Forces in tissue morphogenesis and patterning Cell 153 2013 948 962 23706734
- Henkes S. Fily Y. Marchetti M.C. Active jamming: self-propelled soft particles at high density Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 84 2011 040301 22181078
- Iioka H. Ueno N. Kinoshita N. Essential role of MARCKS in cortical actin dynamics during gastrulation movements J. Cell Biol. 164 2004 169 174 14718521 PMC2172330
- Iyer K.V. Piscitello-Gómez R. Paijmans J. Jülicher F. Eaton S. Epithelial Viscoelasticity Is Regulated by Mechanosensitive E-cadherin Turnover Curr. Biol. 29 2019 578 591.e5 30744966
- Jacobs D.J. Thorpe M.F. Generic rigidity percolation: The pebble game Phys. Rev. Lett. 75 1995 4051 4054 10059802
- Jacobs D.J. Thorpe M.F. Generic rigidity percolation in two dimensions Phys. Rev. E Stat. Phys. Plasmas Fluids Relat. Interdiscip. Topics 53 1996 3682 3693 9964678
- Jorjadze I. Pontani L.-L. Newhall K.A. Brujić J. Attractive emulsion droplets probe the phase diagram of jammed granular matter Proc. Natl. Acad. Sci. USA 108 2011 4286 4291 21368191 PMC3060222
- Keller P.J. Schmidt A.D. Wittbrodt J. Stelzer E.H.K. Reconstruction of Zebrafish Early Embryonic Development by Scanned Light Sheet Microscopy Science 322 2008 1065 1069 18845710
- Kim S. Pochitaloff M. Camp O. Embryonic Tissues as Active Foams bioRxiv 2020 10.1101/2020.06.17.157909 PMC8336761 34367313 · DOI
- Kimmel C.B. Law R.D. Cell lineage of zebrafish blastomeres. I. Cleavage pattern and cytoplasmic bridges between cells Dev. Biol. 108 1985 78 85 3972182
- Koeze D.J. Tighe B.P. Sticky Matters: Jamming and Rigid Cluster Statistics with Attractive Particle Interactions Phys. Rev. Lett. 121 2018 188002 30444395
- Kokic M. Iannini A. Villa-Fombuena G. Casares F. Iber D. Minimisation of surface energy drives apical epithelial organisation and gives rise to Lewis’ law bioRxiv 2019 10.1101/590729 · DOI
- Krajnc M. Dasgupta S. Ziherl P. Prost J. Fluidization of epithelial sheets by active cell rearrangements Phys. Rev. E 98 2018 022409 30253464
- Krieg M. Arboleda-Estudillo Y. Puech P.H. Käfer J. Graner F. Müller D.J. Heisenberg C.P. Tensile forces govern germ-layer organization in zebrafish Nat. Cell Biol. 10 2008 429 436 18364700
- Krotov D. Dubuis J.O. Gregor T. Bialek W. Morphogenesis at criticality Proc. Natl. Acad. Sci. USA 111 2014 3683 3688 24516161 PMC3956198
- Lois G. Blawzdziewicz J. O’Hern C.S. Jamming transition and new percolation universality classes in particulate systems with attraction Phys. Rev. Lett. 100 2008 028001 18232929
- Maître J.-L. Berthoumieux H. Krens S.F.G. Salbreux G. Julicher F. Paluch E. Heisenberg C.-P. Adhesion Functions in Cell Sorting by Mechanically Coupling the Cortices of Adhering Cells Science 338 2012 253 256 22923438
- Maître J.-L. Niwayama R. Turlier H. Nédélec F. Hiiragi T. Pulsatile cell-autonomous contractility drives compaction in the mouse embryo Nat. Cell Biol. 17 2015 849 855 26075357
- Makita R. Mizuno T. Koshida S. Kuroiwa A. Takeda H. Zebrafish wnt11: pattern and regulation of the expression by the yolk cell and No tail activity Mech. Dev. 71 1998 165 176 9507106
- Manning M.L. Foty R.A. Steinberg M.S. Schoetz E.-M. Coaction of intercellular adhesion and cortical tension specifies tissue surface tension Proc. Natl. Acad. Sci. USA 107 2010 12517 12522 20616053 PMC2906578
- Miroshnikova Y.A. Le H.Q. Schneider D. Thalheim T. Rübsam M. Bremicker N. Polleux J. Kamprad N. Tarantola M. Wang I. Adhesion forces and cortical tension couple cell proliferation and differentiation to drive epidermal stratification Nat. Cell Biol. 20 2018 69 80 29230016
- Mongera A. Rowghanian P. Gustafson H.J. Shelton E. Kealhofer D.A. Carn E.K. Serwane F. Lucio A.A. Giammona J. Campàs O. A fluid-to-solid jamming transition underlies vertebrate body axis elongation Nature 561 2018 401 405 30185907 PMC6148385
- Morita H. Grigolon S. Bock M. Krens S.F.G. Salbreux G. Heisenberg C.P. The Physical Basis of Coordinated Tissue Spreading in Zebrafish Gastrulation Dev. Cell 40 2017 354 366.e4 28216382 PMC5364273
- Newman M.E.J. Strogatz S.H. Watts D.J. Random graphs with arbitrary degree distributions and their applications Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 64 2001 026118 11497662
- Okuda S. Inoue Y. Eiraku M. Adachi T. Sasai Y. Vertex dynamics simulations of viscosity-dependent deformation during tissue morphogenesis Biomech. Model. Mechanobiol. 14 2015 413 425 25227116
- Olivier N. Luengo-Oroz M.A. Duloquin L. Faure E. Savy T. Veilleux I. Solinas X. Debarre D. Bourgine P. Santos A.). Cell Lineage Reconstruction of Early Zebrafish Embryos Using Label-Free Nonlinear Microscopy Science 329 2010 967 971 20724640
- Oswald L. Grosser S. Smith D.M. Käs J.A. Jamming transitions in cancer J. Phys. D. Appl. Physiol. 50 2017 483001 PMC5884432 29628530
- Park J.A. Kim J.H. Bi D. Mitchel J.A. Qazvini N.T. Tantisira K. Park C.Y. McGill M. Kim S.H. Gweon B. Unjamming and cell shape in the asthmatic airway epithelium Nat. Mater. 14 2015 1040 1048 26237129 PMC4666305
- Petridou N.I. Heisenberg C.-P. Tissue rheology in embryonic organization EMBO J. 38 2019 e102497 31512749 PMC6792012
- Petridou N.I. Grigolon S. Salbreux G. Hannezo E. Heisenberg C.P. Fluidization-mediated tissue spreading by mitotic cell rounding and non-canonical Wnt signalling Nat. Cell Biol. 21 2019 169 178 30559456
- Pontani L.-L. Jorjadze I. Viasnoff V. Brujic J. Biomimetic emulsions reveal the effect of mechanical forces on cell–cell adhesion Proc. Natl. Acad. Sci. USA 109 2012 9839 9844 22660932 PMC3382526
- Ranft J. Basan M. Elgeti J. Joanny J.-F. Prost J. Jülicher F. Fluidization of tissues by cell division and apoptosis Proc. Natl. Acad. Sci. USA 107 2010 20863 20868 21078958 PMC3000289
- Recho P. Hallou A. Hannezo E. Theory of mechanochemical patterning in biphasic biological tissues Proc. Natl. Acad. Sci. USA 116 2019 5344 5349 30819884 PMC6431232
- Saadaoui M. Rocancourt D. Roussel J. Corson F. Gros J. A tensile ring drives tissue flows to shape the gastrulating amniote embryo Science 367 2020 453 458 31974255
- Sadati M. Taheri Qazvini N. Krishnan R. Park C.Y. Fredberg J.J. Collective migration and cell jamming Differentiation 86 2013 121 125 23791490 PMC3795803
- Schwayer C. Shamipour S. Pranjic-Ferscha K. Schauer A. Balda M. Tada M. Matter K. Heisenberg C.-P. Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow Cell 179 2019 937 952.e18 31675500
- Sepúlveda N. Petitjean L. Cochet O. Grasland-Mongrain E. Silberzan P. Hakim V. Collective cell motion in an epithelial sheet can be quantitatively described by a stochastic interacting particle model PLoS Comput. Biol. 9 2013 e1002944 23505356 PMC3591275
- Shamipour S. Kardos R. Xue S.-L. Hof B. Hannezo E. Heisenberg C.-P. Bulk Actin Dynamics Drive Phase Segregation in Zebrafish Oocytes Cell 177 2019 1463 1479.e18 31080065
- Siber A. Ziherl P. Cellular patterns 2017 CRC Press
- Solé R. Phase Transitions 2011 Princeton University Press
- Stanley H.E. Introduction to Phase Transitions and Critical Phenomena 1971 Oxford University Press
- Tetley R.J. Staddon M.F. Heller D. Hoppe A. Banerjee S. Mao Y. Tissue fluidity promotes epithelial wound healing Nat. Phys. 15 2019 1195 1203 31700525 PMC6837871
- Thisse C. Thisse B. Halpern M.E. Postlethwait J.H. Goosecoid expression in neurectoderm and mesendoderm is disrupted in zebrafish cyclops gastrulas Dev. Biol. 164 1994 420 429 8045345
- Turlier H. Audoly B. Prost J. Joanny J.-F. Furrow constriction in animal cell cytokinesis Biophys. J. 106 2014 114 123 24411243 PMC3907238
- van Hecke M. Jamming of soft particles: geometry, mechanics, scaling and isostaticity J. Phys. Condens. Matter 22 2010 033101 21386274
- Wang X. Merkel M. Sutter L.B. Erdemci-Tandogan G. Manning M.L. Kasza K.E. Anisotropy links cell shapes to tissue flow during convergent extension Proc. Natl. Acad. Sci. USA 117 2020 13541 13551 32467168 PMC7306759
- Zhang M. Kothari P. Mullins M. Lampson M.A. Regulation of zygotic genome activation and DNA damage checkpoint acquisition at the mid-blastula transition Cell Cycle 13 2014 3828 3838 25558827 PMC4614548
- Zhang L. Rocklin D.Z. Chen B.G. Mao X. Rigidity percolation by next-nearest-neighbor bonds on generic and regular isostatic lattices Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 91 2015 032124 25871071
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- Authors
- Petridou, N. I., Corominas-Murtra, B., Heisenberg, C.-P., & Hannezo, E.
- Affiliations
- Institute of Science and Technology Austria (AT)
- Corresponding author
- Heisenberg, Carl-Philipp
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2021-04
- Volume
- 184
- Issue
- 7
- Pages
- 1914-1928.e19
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC8055543
- OpenAlex
- W3138361816
- Cited by
- 222
- References
- 4
- Citations by year
- 2026: 51 · 2025: 46 · 2024: 41 · 2023: 28 · 2022: 34 · 2021: 19 · 2020: 2 · 2019: 1
- FWCI
- 15.92
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- European Research Council (742573, 851288)
- Austrian Science Fund (V 736-B26)
- European Commission
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Physical Sciences › Engineering › Mechanical Engineering › Advanced Materials and Mechanics
- Physical Sciences › Physics and Astronomy › Condensed Matter Physics › Theoretical and Computational Physics
- Keywords
- rigidity percolation, cell connectivity, cell adhesion, tissue rheology, flow index, percolation theory, morphogenesis
- MeSH terms
- Animals, Blastoderm, Cell Adhesion, Embryo, Nonmammalian, Rheology, Viscosity, Zebrafish, Cadherins, Embryonic Development, Morpholinos
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