Abstract
Cell motion is crucial in human health and development. Cells may migrate individually or in highly coordinated groups. Cell motion results from complex intra- and extra-cellular mechanochemical interactions. Computational models have become a powerful tool to shed light on the mechanisms that regulate cell migration. The phase-field method is an emerging modeling technique that permits a simple and direct formulation of the moving cell problem and the interaction between the cell and its environment. This paper intends to be a comprehensive review of phase-field models of individual and collective cell migration. We describe a numerical implementation, based on isogeometric analysis, which successfully deals with the challenges associated with phase-field problems. We present numerical simulations that illustrate the unique capabilities of the phase-field approach for cell migration. In particular, we show 2D and 3D simulations of individual cell migration in confined and fibrous environments that highlight the mechanochemical interplay between the cell and the extracellular environment. We also show 2D simulations of cell co-attraction in non-confluent multicellular systems, in which the use of the phase-field method is crucial to capture the dynamics of the multicellular system.
This is a preview of subscription content, access via your institution.

Adapted from [5]


Adapted from [71]

Adapted from [71]






Reproduced from [116]. (Color figure online)







Notes
- 1.
The lipid molecules possess one end with hydrophilic properties and the other end with hydrophobic properties.
- 2.
ATP hydrolysis is a molecular reaction that produces mechanical energy from chemical energy.
- 3.
Chemokines are signaling proteins secreted by the cells.
- 4.
- 5.
In a Hele-Shaw cell [160], viscous forces can be approximated by \(-\kappa {\mathbf {u}}\), where \(\kappa\) is a constant.
- 6.
References
- 1.
Akiyama M, Sushida T, Ishida S, Haga H (2017) Mathematical model of collective cell migrations based on cell polarity. Dev Growth Differ 59(5):471–490
- 2.
Alaimo F, Praetorius S, Voigt A (2016) A microscopic field theoretical approach for active systems. New J Phys 18(8):083008
- 3.
Alaimo F, Voigt A (2018) Microscopic field-theoretical approach for mixtures of active and passive particles. Phys Rev E 98:032605
- 4.
Aland S, Hatzikirou H, Lowengrub J, Voigt A (2015) A mechanistic collective cell model for epithelial colony growth and contact inhibition. Biophys J 109(7):1347–1357
- 5.
Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2007) Molecular biology of the cell. Garland Science, New York
- 6.
Allen SM, Cahn JW (1979) A microscopic theory for antiphase boundary motion and its application to antiphase domain coarsening. Acta Metall 27(6):1085–1095
- 7.
Allena R, Aubry D (2012) Run-and-tumble or look-and-run? A mechanical model to explore the behavior of a migrating amoeboid cell. J Theor Biol 306:15–31
- 8.
Allena R, Maini P (2014) Reaction-diffusion finite element model of lateral line primordium migration to explore cell leadership. Bull Math Biol 76(12):3028–3050
- 9.
Alonso S, Stange M, Beta C (2018) Modeling random crawling, membrane deformation and intracellular polarity of motile amoeboid cells. PLoS ONE 13(8):e0201977
- 10.
Alt S, Ganguly P, Salbreux G (2017) Vertex models: from cell mechanics to tissue morphogenesis. Philos Trans R Soc B Biol Sci 372(1720):20150520
- 11.
Alt W, Dembo M (1999) Cytoplasm dynamics and cell motion: two-phase flow models. Math Biosci 156(1):207–228
- 12.
Anderson DM, McFadden GB, Wheeler AA (1998) Diffuse-interface methods in fluid mechanics. Annu Rev Fluid Mech 30(1):139–165
- 13.
Angelini TE, Hannezo E, Trepat X, Marquez M, Fredberg JJ, Weitz DA (2011) Glass-like dynamics of collective cell migration. Proc Nat Acad Sci 108(12):4714–4719
- 14.
Antonopoulos M, Stamatakos G (2015) In silico neuro-oncology: brownian motion-based mathematical treatment as a potential platform for modeling the infiltration of glioma cells into normal brain tissue. Cancer Inform 14:33–40
- 15.
Atakhani A, Mohammad-Rafiee F, Gholami A (2019) Influence of cross-linking and retrograde flow on formation and dynamics of lamellipodium. PLoS ONE 14(3):e0213810
- 16.
Aubry D, Thiam H, Piel M, Allena R (2015) A computational mechanics approach to assess the link between cell morphology and forces during confined migration. Biomech Model Mechanobiol 14(1):143–157
- 17.
Balay S, Abhyankar S, Adams MF, Brown J, Brune P, Buschelman K, Dalcin L, Dener A, Eijkhout V, Gropp, WD, Karpeyev D, Kaushik D, Knepley MG, May DA, McInnes LC, Mills RT, Munson T, Rupp K, Sanan P, Smith BF, Zampini S, Zhang H, Zhang H (2019) PETSc web page. http://www.mcs.anl.gov/petsc
- 18.
Barnhart E, Lee KC, Allen GM, Theriot JA, Mogilner A (2015) Balance between cell- substrate adhesion and myosin contraction determines the frequency of motility initiation in fish keratocytes. Proc Nat Acad Sci 112(16):5045–5050
- 19.
Barnhart EL, Lee KC, Keren K, Mogilner A, Theriot JA (2011) An adhesion-dependent switch between mechanisms that determine motile cell shape. PLoS Biol 9(5):e1001059
- 20.
Bazilevs Y, Calo VM, Cottrell JA, Evans JA, Hughes T, Lipton S, Scott MA, Sederberg TW (2010) Isogeometric analysis using t-splines. Comput Methods Appl Mech Eng 199(5):229–263
- 21.
Bazilevs Y, Michler C, Calo V, Hughes T (2010) Isogeometric variational multiscale modeling of wall-bounded turbulent flows with weakly enforced boundary conditions on unstretched meshes. Comput Methods Appl Mech Eng 199(13):780–790
- 22.
Bergert M, Chandradoss SD, Desai RA, Paluch E (2012) Cell mechanics control rapid transitions between blebs and lamellipodia during migration. Proc Nat Acad Sci 109(36):14434–14439
- 23.
Bi D, Yang X, Marchetti MC, Manning ML (2016) Motility-driven glass and jamming transitions in biological tissues. Phys Rev X 6(2):021011
- 24.
Biben T, Kassner K, Misbah C (2005) Phase-field approach to three-dimensional vesicle dynamics. Phys Rev E 72(4):041921
- 25.
Biben T, Misbah C (2003) Tumbling of vesicles under shear flow within an advected-field approach. Phys Rev E 67(3):031908
- 26.
Biner SB (2017) Programming phase-field modeling. Springer, New York
- 27.
Boas SE, Jiang Y, Merks RM, Prokopiou SA, Rens EG (2018) Cellular potts model: applications to vasculogenesis and angiogenesis. In: Louis P-Y, Nardi FR (eds) Probabilistic cellular automata. Springer, New York, pp 279–310
- 28.
Borau C, Kim T, Bidone T, García-Aznar JM, Kamm RD (2012) Dynamic mechanisms of cell rigidity sensing: insights from a computational model of actomyosin networks. PLoS ONE 7(11):e49174
- 29.
Bosgraaf L, Van Haastert PJ (2009) Navigation of chemotactic cells by parallel signaling to pseudopod persistence and orientation. PLoS ONE 4(8):e6842
- 30.
Bosgraaf L, Van Haastert PJ (2009) The ordered extension of pseudopodia by amoeboid cells in the absence of external cues. PLoS ONE 4(4):e5253
- 31.
Bottino D, Mogilner A, Roberts T, Stewart M, Oster G (2002) How nematode sperm crawl. J Cell Sci 115(2):367–384
- 32.
Boyer F, Lapuerta C (2006) Study of a three component Cahn–Hilliard flow model. ESAIM Math Model Numer Anal 40(4):653–687
- 33.
Bresler Y, Palmieri B, Grant M (2018) Effects of cell elasticity on the migration behavior of a monolayer of motile cells: sharp interface model. arXiv preprint arXiv:1807.07836
- 34.
Bueno J, Bazilevs Y, Juanes R, Gomez H (2017) Droplet motion driven by tensotaxis. Extreme Mech Lett 13:10–16
- 35.
Cahn JW, Hilliard JE (1958) Free energy of a nonuniform system. I. Interfacial free energy. J Chem Phys 28(2):258–267
- 36.
Camley BA, Rappel WJ (2017) Physical models of collective cell motility: from cell to tissue. J Phys D Appl Phys 50(11):113002
- 37.
Camley BA, Zhang Y, Zhao Y, Li B, Ben-Jacob E, Levine H, Rappel WJ (2014) Polarity mechanisms such as contact inhibition of locomotion regulate persistent rotational motion of mammalian cells on micropatterns. Proc Nat Acad Sci 111(41):14770–14775
- 38.
Camley BA, Zhao Y, Li B, Levine H, Rappel WJ (2013) Periodic migration in a physical model of cells on micropatterns. Phys Rev Lett 111(15):158102
- 39.
Camley BA, Zhao Y, Li B, Levine H, Rappel WJ (2017) Crawling and turning in a minimal reaction-diffusion cell motility model: coupling cell shape and biochemistry. Phys Rev E 95(1):012401
- 40.
Camley BA, Zimmermann J, Levine H, Rappel WJ (2016) Collective signal processing in cluster chemotaxis: roles of adaptation, amplification, and co-attraction in collective guidance. PLoS Comput Biol 12(7):e1005008
- 41.
Campbell EJ, Bagchi P (2018) A computational model of amoeboid cell motility in the presence of obstacles. Soft Matter 14(28):5741–5763
- 42.
Cao Y, Karmakar R, Ghabache E, Gutierrez E, Zhao Y, Groisman A, Levine H, Camley BA, Rappel WJ (2019) Cell motility dependence on adhesive wetting. Soft Matter 15:2043–2050
- 43.
Cardamone L, Laio A, Torre V, Shahapure R, DeSimone A (2011) Cytoskeletal actin networks in motile cells are critically self-organized systems synchronized by mechanical interactions. Proc Nat Acad Sci 108(34):13978–13983
- 44.
Carlsson A (2011) Mechanisms of cell propulsion by active stresses. New J Phys 13(7):073009
- 45.
Casquero H, Bona-Casas C, Gomez H (2017) Nurbs-based numerical proxies for red blood cells and circulating tumor cells in microscale blood flow. Comput Methods Appl Mech Eng 316:646–667
- 46.
Chan CE, Odde DJ (2008) Traction dynamics of filopodia on compliant substrates. Science 322(5908):1687–1691
- 47.
Charras G, Paluch E (2008) Blebs lead the way: how to migrate without lamellipodia. Nat Rev Mol Cell Biol 9(9):730–736
- 48.
Chen LQ (2002) Phase-field models for microstructure evolution. Annu Rev Mater Res 32(1):113–140
- 49.
Choi CK, Vicente-Manzanares M, Zareno J, Whitmore LA, Mogilner A, Horwitz AR (2008) Actin and \(\alpha\)-actinin orchestrate the assembly and maturation of nascent adhesions in a myosin II motor-independent manner. Nat Cell Biol 10(9):1039
- 50.
Chugh P, Clark AG, Smith MB, Cassani DA, Dierkes K, Ragab A, Roux PP, Charras G, Salbreux G, Paluch EK (2017) Actin cortex architecture regulates cell surface tension. Nat Cell Biol 19(6):689–697
- 51.
Chung J, Hulbert G (1993) A time integration algorithm for structural dynamics with improved numerical dissipation: the generalized-\(\alpha\) method. J Appl Mech 60(2):371–375
- 52.
Cogan N, Guy RD (2010) Multiphase flow models of biogels from crawling cells to bacterial biofilms. HFSP J 4(1):11–25
- 53.
Coleman BD, Noll W (1963) The thermodynamics of elastic materials with heat conduction and viscosity. Arch Ration Mech Anal 13(1):167–178
- 54.
Cortese B, Palamà IE, D’Amone S, Gigli G (2014) Influence of electrotaxis on cell behaviour. Integr Biol 6(9):817–830
- 55.
Cottrell J, Hughes T, Reali A (2007) Studies of refinement and continuity in isogeometric structural analysis. Comput Methods Appl Mech Eng 196(41):4160–4183
- 56.
Dalcin L, Collier N, Vignal P, Crtes A, Calo V (2016) Petiga: a framework for high-performance isogeometric analysis. Comput Methods Appl Mech Eng 308:151–181
- 57.
Danuser G, Allard J, Mogilner A (2013) Mathematical modeling of eukaryotic cell migration: insights beyond experiments. Annu Rev Cell Dev Biol 29:501–528
- 58.
Dawes AT, Edelstein-Keshet L (2007) Phosphoinositides and rho proteins spatially regulate actin polymerization to initiate and maintain directed movement in a one-dimensional model of a motile cell. Biophys J 92(3):744–768
- 59.
Devreotes PN, Bhattacharya S, Edwards M, Iglesias PA, Lampert T, Miao Y (2017) Excitable signal transduction networks in directed cell migration. Annu Rev Cell Dev Biol 33:19.1–19.23
- 60.
Dreher A, Aranson IS, Kruse K (2014) Spiral actin-polymerization waves can generate amoeboidal cell crawling. New J Phys 16(5):055007
- 61.
van Drongelen R, Pal A, Goodrich CP, Idema T (2015) Collective dynamics of soft active particles. Phys Rev E 91(3):032706
- 62.
Elliott CM, Stinner B, Venkataraman C (2012) Modelling cell motility and chemotaxis with evolving surface finite elements. J R Soc Interface 9(76):3027–3044
- 63.
Elosegui-Artola A, Oria R, Chen Y, Kosmalska A, Perez-Gonzalez C, Castro N, Zhu C, Trepat X, Roca-Cusachs P (2016) Mechanical regulation of a molecular clutch defines force transmission and transduction in response to matrix rigidity. Nat Cell Biol 18(5):540–566
- 64.
Emmerich H (2003) The diffuse interface approach in materials science: thermodynamic concepts and applications of phase-field models, vol 73. Springer, New York
- 65.
Escribano J, Sunyer R, Sánchez MT, Trepat X, Roca-Cusachs P, García-Aznar JM (2018) A hybrid computational model for collective cell durotaxis. Biomech Model Mechanobiol 17(4):1037–1052
- 66.
Euteneuer U, Schliwa M (1984) Persistent, directional motility of cells and cytoplasmic fragments in the absence of microtubules. Nature 310(5972):58
- 67.
Farhadifar R, Röper JC, Aigouy B, Eaton S, Jülicher F (2007) The influence of cell mechanics, cell–cell interactions, and proliferation on epithelial packing. Curr Biol 17(24):2095–2104
- 68.
Fletcher AG, Osterfield M, Baker RE, Shvartsman SY (2014) Vertex models of epithelial morphogenesis. Biophys J 106(11):2291–2304
- 69.
Fournier MF, Sauser R, Ambrosi D, Meister JJ, Verkhovsky AB (2010) Force transmission in migrating cells. J Cell Biol 188(2):287–297
- 70.
Frieboes HB, Jin F, Chuang YL, Wise SM, Lowengrub JS, Cristini V (2010) Three-dimensional multispecies nonlinear tumor growth-II: tumor invasion and angiogenesis. J Theor Biol 264(4):1254–1278
- 71.
Friedl P, Wolf K (2003) Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer 3(5):362
- 72.
Friedl P, Wolf K (2009) Plasticity of cell migration: a multiscale tuning model. J Cell Biol 188:11
- 73.
Fuller D, Chen W, Adler M, Groisman A, Levine H, Rappel WJ, Loomis WF (2010) External and internal constraints on eukaryotic chemotaxis. Proc Nat Acad Sci 107(21):9656–9659
- 74.
Gail MH, Boone CW (1970) The locomotion of mouse fibroblasts in tissue culture. Biophys J 10(10):980–993
- 75.
Gamba A, de Candia A, Di Talia S, Coniglio A, Bussolino F, Serini G (2005) Diffusion-limited phase separation in eukaryotic chemotaxis. Proc Nat Acad Sci USA 102(47):16927–16932
- 76.
Giomi L, DeSimone A (2014) Spontaneous division and motility in active nematic droplets. Phys Rev Lett 112(14):147802
- 77.
Gomez H, Bures M, Moure A (2019) A review on computational modelling of phase-transition problems. Philos Trans R Soc A 377(2143):20180203
- 78.
Gómez H, Calo VM, Bazilevs Y, Hughes TJ (2008) Isogeometric analysis of the Cahn–Hilliard phase-field model. Comput Methods Appl Mech Eng 197(49):4333–4352
- 79.
Gomez H, van der Zee KG (2018) Computational phase-field modeling. In: Stein E, Borst R, Hughes TJR (eds) Encyclopedia of computational mechanics, 2nd edn. Wiley, pp 1–35
- 80.
González-Valverde I, García-Aznar JM (2018) Mechanical modeling of collective cell migration: an agent-based and continuum material approach. Comput Methods Appl Mech Eng 337:246–262
- 81.
Gracheva ME, Othmer HG (2004) A continuum model of motility in ameboid cells. Bull Math Biol 66(1):167–193
- 82.
Grimm H, Verkhovsky A, Mogilner A, Meister JJ (2003) Analysis of actin dynamics at the leading edge of crawling cells: implications for the shape of keratocyte lamellipodia. Eur Biophys J 32(6):563–577
- 83.
van Haren J, Charafeddine RA, Ettinger A, Wang H, Hahn KM, Wittmann T (2018) Local control of intracellular microtubule dynamics by eb1 photodissociation. Nat Cell Biol 20(3):252
- 84.
Hatzikirou H, Deutsch A (2008) Cellular automata as microscopic models of cell migration in heterogeneous environments. Curr Top Dev Biol 81:401–434
- 85.
Hecht I, Skoge ML, Charest PG, Ben-Jacob E, Firtel RA, Loomis WF, Levine H, Rappel WJ (2011) Activated membrane patches guide chemotactic cell motility. PLoS Comput Biol 7(6):e1002044
- 86.
Heck T, Smeets B, Vanmaercke S, Bhattacharya P, Odenthal T, Ramon H, Van Oosterwyck H, Van Liedekerke P (2017) Modeling extracellular matrix viscoelasticity using smoothed particle hydrodynamics with improved boundary treatment. Comput Methods Appl Mech Eng 322:515–540
- 87.
Holmes WR, Edelstein-Keshet L (2012) A comparison of computational models for eukaryotic cell shape and motility. PLoS Comput Biol 8(12):e1002793
- 88.
Honda H (1983) Geometrical models for cells in tissues. In: Bourne GH, Danielli JF, Jeon KW (eds) International review of cytology. vol 81. Elsevier, pp 191–248
- 89.
Hughes TJ, Cottrell JA, Bazilevs Y (2005) Isogeometric analysis: cad, finite elements, nurbs, exact geometry and mesh refinement. Comput Methods Appl Mech Eng 194(39):4135–4195
- 90.
Iglesias PA, Devreotes PN (2008) Navigating through models of chemotaxis. Curr Opin Cell Biol 20(1):35–40
- 91.
Iglesias PA, Devreotes PN (2012) Biased excitable networks: how cells direct motion in response to gradients. Curr Opin Cell Biol 24(2):245–253
- 92.
Insall RH (2010) Understanding eukaryotic chemotaxis: a pseudopod-centred view. Nat Rev Mol Cell Biol 11(6):453
- 93.
Jansen KE, Whiting CH, Hulbert GM (2000) A generalized-\(\alpha\) method for integrating the filtered navier-stokes equations with a stabilized finite element method. Comput Methods Appl Mech Eng 190(3):305–319
- 94.
Jiang J, Garikipati K, Rudraraju S (2019) A diffuse interface framework for modeling the evolution of multi-cell aggregates as a soft packing problem driven by the growth and division of cells. Bull Math Biol 81:1–19
- 95.
Joanny JF, Prost J (2009) Active gels as a description of the actin-myosin cytoskeleton. HFSP J 3(2):94–104
- 96.
Jurado C, Haserick JR, Lee J (2005) Slipping or gripping? Fluorescent speckle microscopy in fish keratocytes reveals two different mechanisms for generating a retrograde flow of actin. Mol Biol Cell 16(2):507–518
- 97.
Keller EF, Segel LA (1971) Model for chemotaxis. J Theor Biol 30(2):225–234
- 98.
Keren K, Pincus Z, Allen GM, Barnhart EL, Marriott G, Mogilner A, Theriot JA (2008) Mechanism of shape determination in motile cells. Nature 453(7194):475
- 99.
Kim MC, Whisler J, Silberberg YR, Kamm RD, Asada HH (2015) Cell invasion dynamics into a three dimensional extracellular matrix fibre network. PLoS Comput Biol 11(10):e1004535
- 100.
Kim T (2015) Determinants of contractile forces generated in disorganized actomyosin bundles. Biomech Model Mechanobiol 14(2):345–355
- 101.
Kim T, Hwang W, Kamm R (2009) Computational analysis of a cross-linked actin-like network. Exp Mech 49(1):91–104
- 102.
Kockelkoren J, Levine H, Rappel WJ (2003) Computational approach for modeling intra-and extracellular dynamics. Phys Rev E 68(3):037702
- 103.
Kulawiak DA, Camley BA, Rappel WJ (2016) Modeling contact inhibition of locomotion of colliding cells migrating on micropatterned substrates. PLoS Comput Biol 12(12):1–25
- 104.
Kuusela E, Alt W (2009) Continuum model of cell adhesion and migration. J Math Biol 58(1–2):135
- 105.
Lämmermann T, Sixt M (2009) Mechanical modes of amoeboid-cell migration. Curr Opin Cell Biol 21(5):636–644
- 106.
Larripa K, Mogilner A (2006) Transport of a 1D viscoelastic actin-myosin strip of gel as a model of a crawling cell. Physica A 372(1):113–123
- 107.
Lee CF, Brangwynne CP, Gharakhani J, Hyman AA, Jülicher F (2013) Spatial organization of the cell cytoplasm by position-dependent phase separation. Phys Rev Lett 111(8):088101
- 108.
Lee Y, Kouvroukoglou S, McIntire LV, Zygourakis K (1995) A cellular automaton model for the proliferation of migrating contact-inhibited cells. Biophys J 69(4):1284–1298
- 109.
Levchenko A, Iglesias PA (2002) Models of eukaryotic gradient sensing: application to chemotaxis of amoebae and neutrophils. Biophys J 82(1):50–63
- 110.
Levine H, Kessler DA, Rappel WJ (2006) Directional sensing in eukaryotic chemotaxis: a balanced inactivation model. Proc Nat Acad Sci 103(26):9761–9766
- 111.
Li X, Edwards M, Swaney KF, Singh N, Bhattacharya S, Borleis J, Long Y, Iglesias PA, Chen J, Devreotes PN (2018) Mutually inhibitory RAS-PI(3,4)P2 feedback loops mediate cell migration. Proc Nat Acad Sci 115(39):E9125–E9134
- 112.
Li X, Lowengrub J, Rätz A, Voigt A (2009) Solving PDES in complex geometries: a diffuse domain approach. Commun Math Sci 7(1):81
- 113.
Lin SZ, Li B, Lan G, Feng XQ (2017) Activation and synchronization of the oscillatory morphodynamics in multicellular monolayer. Proc Nat Acad Sci 114(31):8157–8162
- 114.
Liu WK, Liu Y, Farrell D, Zhang L, Wang XS, Fukui Y, Patankar N, Zhang Y, Bajaj C, Lee J et al (2006) Immersed finite element method and its applications to biological systems. Comput Methods Appl Mech Eng 195(13):1722–1749
- 115.
Löber J, Ziebert F, Aranson IS (2014) Modeling crawling cell movement on soft engineered substrates. Soft Matter 10(9):1365–1373
- 116.
Löber J, Ziebert F, Aranson IS (2015) Collisions of deformable cells lead to collective migration. Sci Rep 5:9172
- 117.
Lorenzo G, Scott M, Tew K, Hughes T, Gomez H (2017) Hierarchically refined and coarsened splines for moving interface problems, with particular application to phase-field models of prostate tumor growth. Comput Methods Appl Mech Eng 319:515–548
- 118.
MacDonald G, Mackenzie JA, Nolan M, Insall R (2016) A computational method for the coupled solution of reaction-diffusion equations on evolving domains and manifolds: application to a model of cell migration and chemotaxis. J Comput Phys 309:207–226
- 119.
Mak M, Spill F, Kamm RD, Zaman MH (2016) Single-cell migration in complex microenvironments: mechanics and signaling dynamics. J Biomech Eng 138(2):021004
- 120.
Malet-Engra G, Yu W, Oldani A, Rey-Barroso J, Gov NS, Scita G, Dupré L (2015) Collective cell motility promotes chemotactic prowess and resistance to chemorepulsion. Curr Biol 25(2):242–250
- 121.
Malik-Garbi M, Ierushalmi N, Jansen S, Abu-Shah E, Goode BL, Mogilner A, Keren K (2019) Scaling behaviour in steady-state contracting actomyosin networks. Nat Phys 15:509–516
- 122.
Mallet DG, De Pillis LG (2006) A cellular automata model of tumor-immune system interactions. J Theor Biol 239(3):334–350
- 123.
Marée AF, Grieneisen VA, Edelstein-Keshet L (2012) How cells integrate complex stimuli: the effect of feedback from phosphoinositides and cell shape on cell polarization and motility. PLoS Comput Biol 8(3):e1002402
- 124.
Marée AF, Hogeweg P (2001) How amoeboids self-organize into a fruiting body: multicellular coordination in dictyostelium discoideum. Proc Nat Acad Sci 98(7):3879–3883
- 125.
Marth W, Praetorius S, Voigt A (2015) A mechanism for cell motility by active polar gels. J R Soc Interface 12(107):20150161
- 126.
Marth W, Voigt A (2014) Signaling networks and cell motility: a computational approach using a phase field description. J Math Biol 69(1):91–112
- 127.
Marth W, Voigt A (2016) Collective migration under hydrodynamic interactions: a computational approach. Interface Focus 6(5):20160037
- 128.
Meineke FA, Potten CS, Loeffler M (2001) Cell migration and organization in the intestinal crypt using a lattice-free model. Cell Prolif 34(4):253–266
- 129.
Meinhardt H (1999) Orientation of chemotactic cells and growth cones: models and mechanisms. J Cell Sci 112(17):2867–2874
- 130.
Mizuhara MS, Berlyand L, Aranson IS (2017) Minimal model of directed cell motility on patterned substrates. Phys Rev E 96(5):052408
- 131.
Mogilner A, Manhart A (2018) Intracellular fluid mechanics: coupling cytoplasmic flow with active cytoskeletal gel. Annu Rev Fluid Mech 50:347–370
- 132.
Mokbel D, Abels H, Aland S (2018) A phase-field model for fluid-structure interaction. J Comput Phys 372:823–840
- 133.
Molina JJ, Yamamoto R (2019) Modeling the mechanosensitivity of fast-crawling cells on cyclically stretched substrates. Soft Matter 15(4):683–698
- 134.
Mori Y, Jilkine A, Edelstein-Keshet L (2008) Wave-pinning and cell polarity from a bistable reaction-diffusion system. Biophys J 94(9):3684–3697
- 135.
Moure A, Gomez H (2016) Computational model for amoeboid motion: coupling membrane and cytosol dynamics. Phys Rev E 94(4):042423
- 136.
Moure A, Gomez H (2017) Phase-field model of cellular migration: three-dimensional simulations in fibrous networks. Comput Methods Appl Mech Eng 320:162–197
- 137.
Moure A, Gomez H (2018) Three-dimensional simulation of obstacle-mediated chemotaxis. Biomech Model Mechanobiol 17(5):1243–1268
- 138.
Mueller R, Yeomans JM, Doostmohammadi A (2019) Emergence of active nematic behavior in monolayers of isotropic cells. Phys Rev Lett 122(4):048004
- 139.
Najem S, Grant M (2016) Phase-field model for collective cell migration. Phys Rev E 93(5):052405
- 140.
Nava-Sedeño J, Hatzikirou H, Peruani F, Deutsch A (2017) Extracting cellular automaton rules from physical Langevin equation models for single and collective cell migration. J Math Biol 75(5):1075–1100
- 141.
Neilson MP, Veltman DM, van Haastert PJ, Webb SD, Mackenzie JA, Insall RH (2011) Chemotaxis: a feedback-based computational model robustly predicts multiple aspects of real cell behaviour. PLoS Biol 9(5):e1000618
- 142.
Nonomura M (2012) Study on multicellular systems using a phase field model. PLoS ONE 7(4):e33501
- 143.
Novak IL, Gao F, Choi YS, Resasco D, Schaff JC, Slepchenko BM (2007) Diffusion on a curved surface coupled to diffusion in the volume: application to cell biology. J Comput Phys 226(2):1271–1290
- 144.
Oria R, Wiegand T, Escribano J, Elosegui-Artola A, Uriarte JJ, Moreno-Pulido C, Platzman I, Delcanale P, Albertazzi L, Navajas D et al (2017) Force loading explains spatial sensing of ligands by cells. Nature 552(7684):219
- 145.
Otsuji M, Ishihara S, Kaibuchi K, Mochizuki A, Kuroda S et al (2007) A mass conserved reaction-diffusion system captures properties of cell polarity. PLoS Comput Biol 3(6):e108
- 146.
Palmieri B, Bresler Y, Wirtz D, Grant M (2015) Multiple scale model for cell migration in monolayers: elastic mismatch between cells enhances motility. Sci Rep 5:11745
- 147.
Palsson E, Othmer HG (2000) A model for individual and collective cell movement in dictyostelium discoideum. Proc Nat Acad Sci 97(19):10448–10453
- 148.
Petitjean L, Reffay M, Grasland-Mongrain E, Poujade M, Ladoux B, Buguin A, Silberzan P (2010) Velocity fields in a collectively migrating epithelium. Biophys J 98(9):1790–1800
- 149.
Peyret G, Mueller R, d’Alessandro J, Begnaud S, Marcq P, Mege RM, Yeomans J, Doostmohammadi A, Ladoux B (2018) Sustained oscillations of epithelial cell sheets. bioRxiv 492082
- 150.
Potel MJ, Mackay SA (1979) Preaggregative cell motion in dictyostelium. J Cell Sci 36(1):281–309
- 151.
Poujade M, Grasland-Mongrain E, Hertzog A, Jouanneau J, Chavrier P, Ladoux B, Buguin A, Silberzan P (2007) Collective migration of an epithelial monolayer in response to a model wound. Proc Nat Acad Sci 104(41):15988–15993
- 152.
Provatas N, Elder K (2011) Phase-field methods in materials science and engineering. Wiley, New York
- 153.
Rapanan JL, Cooper KE, Leyva KJ, Hull EE (2014) Collective cell migration of primary zebrafish keratocytes. Exp Cell Res 326(1):155–165
- 154.
Reeves C, Winkler B, Ziebert F, Aranson IS (2018) Rotating lamellipodium waves in polarizing cells. Commun Phys 1(1):73
- 155.
Rey R, Garcia-Aznar J (2013) A phenomenological approach to modelling collective cell movement in 2D. Biomech Model Mechanobiol 12(6):1089–1100
- 156.
Ribeiro F, Gómez-Benito M, Folgado J, Fernandes P, García-Aznar J (2017) Computational model of mesenchymal migration in 3D under chemotaxis. Comput Methods Biomech Biomed Eng 20(1):59–74
- 157.
Romanczuk P, Bär M, Ebeling W, Lindner B, Schimansky-Geier L (2012) Active brownian particles. Eur Phys J Spec Top 202(1):1–162
- 158.
Roussos ET, Condeelis JS, Patsialou A (2011) Chemotaxis in cancer. Nat Rev Cancer 11(8):573
- 159.
Rubinstein B, Fournier MF, Jacobson K, Verkhovsky AB, Mogilner A (2009) Actin-myosin viscoelastic flow in the keratocyte lamellipod. Biophys J 97(7):1853–1863
- 160.
Saffman PG, Taylor GI (1958) The penetration of a fluid into a porous medium or hele-shaw cell containing a more viscous liquid. Proc R Soc Lond A 245(1242):312–329
- 161.
Schillinger D, Dede L, Scott MA, Evans JA, Borden MJ, Rank E, Hughes TJ (2012) An isogeometric design-through-analysis methodology based on adaptive hierarchical refinement of nurbs, immersed boundary methods, and t-spline cad surfaces. Comput Methods Appl Mech Eng 249:116–150
- 162.
Schmidt R, Wüchner R, Bletzinger KU (2012) Isogeometric analysis of trimmed nurbs geometries. Comput Methods Appl Mech Eng 241:93–111
- 163.
Scianna M, Preziosi L, Wolf K (2013) A cellular potts model simulating cell migration on and in matrix environments. Math Biosci Eng 10(1):235–261
- 164.
Scott MA, Thomas DC, Evans EJ (2014) Isogeometric spline forests. Comput Methods Appl Mech Eng 269:222–264
- 165.
Shao D, Levine H, Rappel WJ (2012) Coupling actin flow, adhesion, and morphology in a computational cell motility model. Proc Nat Acad Sci 109(18):6851–6856
- 166.
Shao D, Rappel WJ, Levine H (2010) Computational model for cell morphodynamics. Phys Rev Lett 105(10):108104
- 167.
Shi C, Huang CH, Devreotes PN, Iglesias PA (2013) Interaction of motility, directional sensing, and polarity modules recreates the behaviors of chemotaxing cells. PLoS Comput Biol 9(7):e1003122
- 168.
Shields JD, Fleury ME, Yong C, Tomei AA, Randolph GJ, Swartz MA (2007) Autologous chemotaxis as a mechanism of tumor cell homing to lymphatics via interstitial flow and autocrine CCR7 signaling. Cancer Cell 11(6):526–538
- 169.
Shin Y, Brangwynne CP (2017) Liquid phase condensation in cell physiology and disease. Science 357(6357):eaaf4382
- 170.
Song J, Kim D (2010) Three-dimensional chemotaxis model for a crawling neutrophil. Phys Rev E 82(5):051902
- 171.
Song L, Nadkarni SM, Bödeker HU, Beta C, Bae A, Franck C, Rappel WJ, Loomis WF, Bodenschatz E (2006) Dictyostelium discoideum chemotaxis: threshold for directed motion. Eur J Cell Biol 85(9):981–989
- 172.
Strychalski W, Copos CA, Lewis OL, Guy RD (2015) A poroelastic immersed boundary method with applications to cell biology. J Comput Phys 282:77–97
- 173.
Strychalski W, Guy RD (2012) A computational model of bleb formation. Math Med Biol J IMA 30(2):115–130
- 174.
Subramanian K, Narang A (2004) A mechanistic model for eukaryotic gradient sensing: spontaneous and induced phosphoinositide polarization. J Theor Biol 231(1):49–67
- 175.
Sunyer R, Conte V, Escribano J, Elosegui-Artola A, Labernadie A, Valon L, Navajas D, García-Aznar JM, Muñoz JJ, Roca-Cusachs P et al (2016) Collective cell durotaxis emerges from long-range intercellular force transmission. Science 353(6304):1157–1161
- 176.
Swaney KF, Huang CH, Devreotes PN (2010) Eukaryotic chemotaxis: a network of signaling pathways controls motility, directional sensing, and polarity. Annu Rev Biophys 39:265–289
- 177.
Te Boekhorst V, Preziosi L, Friedl P (2016) Plasticity of cell migration in vivo and in silico. Annu Rev Cell Dev Biol 32:491–526
- 178.
Teigen KE, Li X, Lowengrub J, Wang F, Voigt A (2009) A diffuse-interface approach for modeling transport, diffusion and adsorption/desorption of material quantities on a deformable interface. Commun Math Sci 4(7):1009
- 179.
Theveneau E, Marchant L, Kuriyama S, Gull M, Moepps B, Parsons M, Mayor R (2010) Collective chemotaxis requires contact-dependent cell polarity. Dev Cell 19(1):39–53
- 180.
Thiery JP (2002) Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2(6):442
- 181.
Tjhung E, Marenduzzo D, Cates ME (2012) Spontaneous symmetry breaking in active droplets provides a generic route to motility. Proc Nat Acad Sci 109(31):12381–12386
- 182.
Tjhung E, Tiribocchi A, Marenduzzo D, Cates M (2015) A minimal physical model captures the shapes of crawling cells. Nat Commun 6:5420
- 183.
Tozluoglu M, Tournier AL, Jenkins RP, Hooper S, Bates PA, Sahai E (2013) Matrix geometry determines optimal cancer cell migration strategy and modulates response to interventions. Nat Cell Biol 15(7):751
- 184.
Trepat X, Wasserman MR, Angelini TE, Millet E, Weitz DA, Butler JP, Fredberg JJ (2009) Physical forces during collective cell migration. Nat Phys 5(6):426
- 185.
Truesdell C, Noll W (2004) The non-linear field theories of mechanics. In: Truesdell C, Noll W, Antman SS (eds) The non-linear field theories of mechanics. Springer, New York, pp 1–579
- 186.
Valero C, Javierre E, García-Aznar J, Gómez-Benito M (2014) Nonlinear finite element simulations of injuries with free boundaries: application to surgical wounds. Int J Numer Methods Biomed Eng 30(6):616–633
- 187.
Van Haastert PJ (2010) A stochastic model for chemotaxis based on the ordered extension of pseudopods. Biophys J 99(10):3345–3354
- 188.
Van Haastert PJ, Devreotes PN (2004) Chemotaxis: signalling the way forward. Nat Rev Mol Cell Biol 5(8):626
- 189.
Van Liedekerke P, Palm M, Jagiella N, Drasdo D (2015) Simulating tissue mechanics with agent-based models: concepts, perspectives and some novel results. Comput Part Mech 2(4):401–444
- 190.
Vedel S, Tay S, Johnston DM, Bruus H, Quake SR (2013) Migration of cells in a social context. Proc Nat Acad Sci 110(1):129–134
- 191.
Vedula SRK, Leong MC, Lai TL, Hersen P, Kabla AJ, Lim CT, Ladoux B (2012) Emerging modes of collective cell migration induced by geometrical constraints. Proc Nat Acad Sci 109(32):12974–12979
- 192.
Vermolen F, Gefen A (2013) A phenomenological model for chemico-mechanically induced cell shape changes during migration and cell–cell contacts. Biomech Model Mechanobiol 20:1–23
- 193.
Vermolen F, Javierre E (2012) A finite-element model for healing of cutaneous wounds combining contraction, angiogenesis and closure. J Math Biol 65(5):967–996
- 194.
Vicente-Manzanares M, Newell-Litwa K, Bachir AI, Whitmore LA, Horwitz AR (2011) Myosin IIA/IIB restrict adhesive and protrusive signaling to generate front-back polarity in migrating cells. J Cell Biol 193(2):381–396
- 195.
Vuong AV, Giannelli C, Jüttler B, Simeon B (2011) A hierarchical approach to adaptive local refinement in isogeometric analysis. Comput Methods Appl Mech Eng 200(49–52):3554–3567
- 196.
Wang X, Du Q (2008) Modelling and simulations of multi-component lipid membranes and open membranes via diffuse interface approaches. J Math Biol 56(3):347–371
- 197.
Wenzel D, Praetorius S, Voigt A (2019) Topological and geometrical quantities in active cellular structures. J Chem Phys 150(16):164108
- 198.
Whitfield CA, Marenduzzo D, Voituriez R, Hawkins RJ (2014) Active polar fluid flow in finite droplets. Eur Phys J E 37(2):8
- 199.
Winkler B, Aranson IS, Ziebert F (2016) Membrane tension feedback on shape and motility of eukaryotic cells. Physica D 318:26–33
- 200.
Wise SM, Lowengrub JS, Frieboes HB, Cristini V (2008) Three-dimensional multispecies nonlinear tumor growthi: model and numerical method. J Theor Biol 253(3):524–543
- 201.
Wu PH, Giri A, Sun SX, Wirtz D (2014) Three-dimensional cell migration does not follow a random walk. Proc Nat Acad Sci 111(11):3949–3954
- 202.
Xi W, Sonam S, Saw TB, Ladoux B, Lim CT (2017) Emergent patterns of collective cell migration under tubular confinement. Nat Commun 8(1):1517
- 203.
Xu J, Vilanova G, Gomez H (2017) Full-scale, three-dimensional simulation of early-stage tumor growth: the onset of malignancy. Comput Methods Appl Mech Eng 314:126–146
- 204.
Yang L, Witten TM, Pidaparti RM (2013) A biomechanical model of wound contraction and scar formation. J Theor Biol 332:228–248
- 205.
Yao M, Goult BT, Klapholz B, Hu X, Toseland CP, Guo Y, Cong P, Sheetz MP, Yan J (2016) The mechanical response of talin. Nat Commun 7:11966
- 206.
Ziebert F, Aranson IS (2013) Effects of adhesion dynamics and substrate compliance on the shape and motility of crawling cells. PLoS ONE 8(5):e64511
- 207.
Ziebert F, Aranson IS (2016) Computational approaches to substrate-based cell motility. npj Comput Mater 2:16019
- 208.
Ziebert F, Swaminathan S, Aranson IS (2011) Model for self-polarization and motility of keratocyte fragments. J R Soc Interface 9(70):1084–1092
- 209.
Zimmermann J, Camley BA, Rappel WJ, Levine H (2016) Contact inhibition of locomotion determines cell–cell and cell-substrate forces in tissues. Proc Nat Acad Sci 113(10):2660–2665
Author information
Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Moure, A., Gomez, H. Phase-Field Modeling of Individual and Collective Cell Migration. Arch Computat Methods Eng 28, 311–344 (2021). https://doi.org/10.1007/s11831-019-09377-1
Received:
Accepted:
Published:
Issue Date: