Continuum Models of Collective Cell Migration.

Collective cell migration plays a central role in tissue development, morphogenesis, wound repair and cancer progression. With the growing realization that physical forces mediate cell motility in development and physiology, a key biological question is how cells integrate molecular activities for force generation on multicellular scales. In this review we discuss recent advances in modeling collective cell migration using quantitative tools and approaches rooted in soft matter physics. We focus on theoretical models of cell aggregates as continuous active media, where the feedback between mechanical forces and regulatory biochemistry gives rise to rich collective dynamical behavior. This class of models provides a powerful predictive framework for the physiological dynamics that underlies many developmental processes, where cells need to collectively migrate like a viscous fluid to reach a target region, and then stiffen to support mechanical stresses and maintain tissue cohesion.

[1]  Wesley R. Legant,et al.  Multidimensional traction force microscopy reveals out-of-plane rotational moments about focal adhesions , 2012, Proceedings of the National Academy of Sciences.

[2]  J. Elgeti,et al.  Detachment and fracture of cellular aggregates , 2013 .

[3]  M. Marchetti,et al.  Contractile stresses in cohesive cell layers on finite-thickness substrates. , 2012, Physical review letters.

[4]  Thomas Lecuit,et al.  Biomechanical regulation of contractility: spatial control and dynamics. , 2012, Trends in cell biology.

[5]  Paul Martin,et al.  Mechanisms of epithelial fusion and repair , 2001, Nature Cell Biology.

[6]  Steinberg,et al.  Liquid properties of embryonic tissues: Measurement of interfacial tensions. , 1994, Physical review letters.

[7]  M. Sheetz,et al.  Cell crawling mediates collective cell migration to close undamaged epithelial gaps , 2012, Proceedings of the National Academy of Sciences.

[8]  Cristian Suarez,et al.  Internetwork competition for monomers governs actin cytoskeleton organization , 2016, Nature Reviews Molecular Cell Biology.

[9]  H Delanoë-Ayari,et al.  4D traction force microscopy reveals asymmetric cortical forces in migrating Dictyostelium cells. , 2010, Physical review letters.

[10]  Christopher S. Chen,et al.  Mechanotransduction in development: a growing role for contractility , 2009, Nature Reviews Molecular Cell Biology.

[11]  M. S. Steinberg,et al.  Embryonic tissues as elasticoviscous liquids. I. Rapid and slow shape changes in centrifuged cell aggregates. , 1978, Journal of cell science.

[12]  C. Heisenberg,et al.  Forces in Tissue Morphogenesis and Patterning , 2013, Cell.

[13]  D. Discher,et al.  Optimal matrix rigidity for stress fiber polarization in stem cells. , 2010, Nature physics.

[14]  B. Ladoux,et al.  Mechanobiology of collective cell behaviours , 2017, Nature Reviews Molecular Cell Biology.

[15]  G. Charras,et al.  Characterizing the mechanics of cultured cell monolayers , 2012, Proceedings of the National Academy of Sciences.

[16]  Colin J. Wiebe,et al.  Mechanical Effects of Cell Anisotropy on Epithelia , 2004, Computer methods in biomechanics and biomedical engineering.

[17]  P. Janmey,et al.  Tissue Cells Feel and Respond to the Stiffness of Their Substrate , 2005, Science.

[18]  M. Rao,et al.  Actomyosin pulsation and flows in an active elastomer with turnover and network remodeling , 2017, Nature Communications.

[19]  M Cristina Marchetti,et al.  Motility-driven glass and jamming transitions in biological tissues. , 2015, Physical Review X.

[20]  G. Forgacs,et al.  Surface tensions of embryonic tissues predict their mutual envelopment behavior. , 1996, Development.

[21]  X. Trepat,et al.  Active wetting of epithelial tissues , 2018, Nature Physics.

[22]  Dominique P. Pioletti,et al.  Computer Methods in Biomechanics and Biomedical Engineering , 2007 .

[23]  Marion Ghibaudo,et al.  Traction forces and rigidity sensing regulate cell functions , 2008 .

[24]  Chwee Teck Lim,et al.  Topological defects in epithelia govern cell death and extrusion , 2017, Nature.

[25]  A. Kabla,et al.  Gap geometry dictates epithelial closure efficiency , 2015, Nature Communications.

[26]  Thomas Lecuit,et al.  Mechanics of Epithelial Tissue Homeostasis and Morphogenesis , 2013, Science.

[27]  Alan R. Lowe,et al.  Local cellular neighborhood controls proliferation in cell competition , 2017, Molecular biology of the cell.

[28]  H Honda,et al.  How much does the cell boundary contract in a monolayered cell sheet? , 1980, Journal of theoretical biology.

[29]  Visar Ajeti,et al.  Cooperation of dual modes of cell motility promotes epithelial stress relaxation to accelerate wound healing , 2018, PLoS Comput. Biol..

[30]  Anh Phuong Le,et al.  Regulation of epithelial cell organization by tuning cell-substrate adhesion. , 2015, Integrative biology : quantitative biosciences from nano to macro.

[31]  Rastko Sknepnek,et al.  Active Vertex Model for cell-resolution description of epithelial tissue mechanics , 2017, PLoS Comput. Biol..

[32]  M. Poujade,et al.  Velocity fields in a collectively migrating epithelium. , 2010, Biophysical journal.

[33]  J. Alcaraz,et al.  Micropatterning of single endothelial cell shape reveals a tight coupling between nuclear volume in G1 and proliferation. , 2008, Biophysical journal.

[34]  Shiladitya Banerjee,et al.  Controlling cell–matrix traction forces by extracellular geometry , 2012, 1211.5075.

[35]  Gabriel Fenteany,et al.  Signaling pathways and cell mechanics involved in wound closure by epithelial cell sheets , 2000, Current Biology.

[36]  P. Forscher,et al.  A novel cytoskeletal structure involved in purse string wound closure and cell polarity maintenance , 1993, The Journal of cell biology.

[37]  Paul Martin,et al.  Actin cables and epidermal movement in embryonic wound healing , 1992, Nature.

[38]  Pierre-François Lenne,et al.  Force generation, transmission, and integration during cell and tissue morphogenesis. , 2011, Annual review of cell and developmental biology.

[39]  E. Dufresne,et al.  Cadherin-based intercellular adhesions organize epithelial cell–matrix traction forces , 2012, Proceedings of the National Academy of Sciences.

[40]  Ulrich S. Schwarz,et al.  Dynamics of Cell Ensembles on Adhesive Micropatterns: Bridging the Gap between Single Cell Spreading and Collective Cell Migration , 2016, PLoS Comput. Biol..

[41]  M. Marchetti,et al.  Propagating Stress Waves During Epithelial Expansion. , 2014, Physical review letters.

[42]  S. Grill,et al.  How Active Mechanics and Regulatory Biochemistry Combine to Form Patterns in Development. , 2017, Annual review of biophysics.

[43]  Mina J. Bissell,et al.  Coherent angular motion in the establishment of multicellular architecture of glandular tissues , 2012, Proceedings of the National Academy of Sciences.

[44]  S. Ramaswamy,et al.  Hydrodynamics of soft active matter , 2013 .

[45]  A. Kabla,et al.  Collective cell migration: leadership, invasion and segregation , 2011, Journal of The Royal Society Interface.

[46]  Jonathon Howard,et al.  Turing's next steps: the mechanochemical basis of morphogenesis , 2011, Nature Reviews Molecular Cell Biology.

[47]  C. M. Edwards,et al.  Force localization in contracting cell layers. , 2011, Physical review letters.

[48]  Xavier Trepat,et al.  Active Tensile Modulus of an Epithelial Monolayer. , 2015, Physical review letters.

[49]  Françoise Brochard-Wyart,et al.  Aspiration , 2019, Differential Diagnosis of Cardiopulmonary Disease.

[50]  Frank Jülicher,et al.  Active gel physics , 2015, Nature Physics.

[51]  Michael F Staddon,et al.  Wound Healing Coordinates Actin Architectures to Regulate Mechanical Work , 2019, Nature Physics.

[52]  Margaret L. Gardel,et al.  Force localization modes in dynamic epithelial colonies , 2018, bioRxiv.

[53]  B. Shraiman,et al.  Active Tension Network model suggests an exotic mechanical state realized in epithelial tissues , 2017, Nature Physics.

[54]  R. Austin,et al.  Force mapping in epithelial cell migration. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[55]  J. Fredberg,et al.  Collective cell guidance by cooperative intercellular forces , 2010, Nature materials.

[56]  J. Casademunt,et al.  Hydrodynamic instabilities, waves and turbulence in spreading epithelia. , 2017, Soft matter.

[57]  Anant Chopra,et al.  Cardiac myocyte remodeling mediated by N-cadherin-dependent mechanosensing. , 2011, American journal of physiology. Heart and circulatory physiology.

[58]  Vicsek,et al.  Novel type of phase transition in a system of self-driven particles. , 1995, Physical review letters.

[59]  G. Charras,et al.  The dynamic mechanical properties of cellularised aggregates. , 2016, Current opinion in cell biology.

[60]  Joachim O Rädler,et al.  Emergence and Persistence of Collective Cell Migration on Small Circular Micropatterns. , 2015, Physical review letters.

[61]  M Cristina Marchetti,et al.  Scaling of traction forces with the size of cohesive cell colonies. , 2011, Physical review letters.

[62]  Pilhwa Lee,et al.  Crawling Cells Can Close Wounds without Purse Strings or Signaling , 2011, PLoS Comput. Biol..

[63]  W. Rappel,et al.  Alignment of cellular motility forces with tissue flow as a mechanism for efficient wound healing , 2013, Proceedings of the National Academy of Sciences.

[64]  Glazier,et al.  Simulation of biological cell sorting using a two-dimensional extended Potts model. , 1992, Physical review letters.

[65]  Patrick W. Oakes,et al.  Disordered actomyosin networks are sufficient to produce cooperative and telescopic contractility , 2016, Nature Communications.

[66]  P. Friedl,et al.  Collective cell migration in morphogenesis, regeneration and cancer , 2009, Nature Reviews Molecular Cell Biology.

[67]  Sean X. Sun,et al.  Coherent motions in confluent cell monolayer sheets. , 2014, Biophysical journal.

[68]  P. Recho,et al.  One-dimensional collective migration of a proliferating cell monolayer. , 2016, Soft matter.

[69]  P. Chavrier,et al.  Collective migration of an epithelial monolayer in response to a model wound , 2007, Proceedings of the National Academy of Sciences.

[70]  Adhesive micropatterns for cells: a microcontact printing protocol. , 2009, Cold Spring Harbor protocols.

[71]  Xavier Trepat,et al.  Quantifying forces in cell biology , 2017, Nature Cell Biology.

[72]  Pascal Silberzan,et al.  Topological defects in confined populations of spindle-shaped cells , 2016, Nature Physics.

[73]  Hannah G. Yevick,et al.  Emergence of collective modes and tri-dimensional structures from epithelial confinement , 2014, Nature Communications.

[74]  Dapeng Bi,et al.  A density-independent rigidity transition in biological tissues , 2014, Nature Physics.

[75]  Len M. Pismen,et al.  A continuum model of epithelial spreading , 2013 .

[76]  David A. Weitz,et al.  Physical forces during collective cell migration , 2009 .

[77]  Louise P. Cramer,et al.  An epithelial cell destined for apoptosis signals its neighbors to extrude it by an actin- and myosin-dependent mechanism , 2001, Current Biology.

[78]  Frank Jülicher,et al.  Fluidization of tissues by cell division and apoptosis , 2010, Proceedings of the National Academy of Sciences.

[79]  G. Oster,et al.  Cell traction models for generating pattern and form in morphogenesis , 1984, Journal of mathematical biology.

[80]  M. Marchetti,et al.  Instabilities and oscillations in isotropic active gels , 2010, 1006.1445.

[81]  Jennifer H. Shin,et al.  Cellular Contraction and Polarization Drive Collective Cellular Motion. , 2016, Biophysical journal.

[82]  Chwee Teck Lim,et al.  Guidance of collective cell migration by substrate geometry. , 2013, Integrative biology : quantitative biosciences from nano to macro.

[83]  S. Grill,et al.  Pattern Formation in Active Fluids , 2011 .

[84]  Rizwan U. Farooqui,et al.  Multiple rows of cells behind an epithelial wound edge extend cryptic lamellipodia to collectively drive cell-sheet movement , 2005, Journal of Cell Science.

[85]  U. Schwarz,et al.  Effect of adhesion geometry and rigidity on cellular force distributions. , 2009, Physical review letters.

[86]  Benoit Ladoux,et al.  Active superelasticity in three-dimensional epithelia of controlled shape , 2018, Nature.

[87]  B. Shraiman,et al.  Mechanical feedback as a possible regulator of tissue growth. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[88]  M. Marchetti,et al.  Generic phases of cross-linked active gels: Relaxation, oscillation and contractility , 2011, 1108.5999.

[89]  M. Théry Wave of migration , 2012, Nature Physics.

[90]  Ulrich S Schwarz,et al.  Cell-ECM traction force modulates endogenous tension at cell–cell contacts , 2011, Proceedings of the National Academy of Sciences.

[91]  Ruth E Baker,et al.  Vertex models of epithelial morphogenesis. , 2014, Biophysical journal.

[92]  Sean X. Sun,et al.  Cytoskeletal Cross-linking and Bundling in Motor-Independent Contraction , 2010, Current Biology.

[93]  J. Fredberg,et al.  Mechanical waves during tissue expansion , 2012, Nature Physics.

[94]  P ? ? ? ? ? ? ? % ? ? ? ? , 1991 .

[95]  M. Marchetti,et al.  Substrate rigidity deforms and polarizes active gels , 2011, 1106.0929.

[96]  X. Trepat,et al.  Effective viscosity and dynamics of spreading epithelia: a solvable model. , 2017, Soft matter.

[97]  Frank Jülicher,et al.  The Influence of Cell Mechanics, Cell-Cell Interactions, and Proliferation on Epithelial Packing , 2007, Current Biology.

[98]  J. Fredberg,et al.  Glass-like dynamics of collective cell migration , 2011, Proceedings of the National Academy of Sciences.

[99]  M Cristina Marchetti,et al.  Geometry regulates traction stresses in adherent cells. , 2014, Biophysical journal.

[100]  B. Ladoux,et al.  Mechanics of epithelial tissues during gap closure. , 2016, Current opinion in cell biology.

[101]  T. Mitchison,et al.  A high-throughput cell migration assay using scratch wound healing, a comparison of image-based readout methods , 2004, BMC biotechnology.

[102]  P. Marcq,et al.  Cell growth, division, and death in cohesive tissues: A thermodynamic approach. , 2017, Physical review. E.

[103]  G. Wayne Brodland,et al.  Forces driving epithelial wound healing , 2014, Nature Physics.

[104]  Falko Ziebert,et al.  Model for self-polarization and motility of keratocyte fragments , 2012, Journal of The Royal Society Interface.

[105]  Jacques Prost,et al.  Homeostatic competition drives tumor growth and metastasis nucleation , 2009, HFSP journal.

[106]  Gaudenz Danuser,et al.  Competition of two distinct actin networks for actin defines a bistable switch for cell polarization , 2015, Nature Cell Biology.

[107]  Chwee Teck Lim,et al.  Mechanics of epithelial closure over non-adherent environments , 2015, Nature Communications.

[108]  M. Marchetti,et al.  Hydrodynamics of isotropic and liquid crystalline active polymer solutions. , 2006, Physical review. E, Statistical, nonlinear, and soft matter physics.

[109]  Brian A. Camley,et al.  Physical models of collective cell motility: from cell to tissue , 2017, Journal of physics D: Applied physics.

[110]  Ulrich S. Schwarz,et al.  Physics of adherent cells , 2013, 1309.2817.

[111]  P. Silberzan,et al.  Border forces and friction control epithelial closure dynamics. , 2014, Biophysical journal.

[112]  Mark Miodownik,et al.  Stress relaxation in epithelial monolayers is controlled by the actomyosin cortex , 2019, Nature physics.

[113]  Sean X. Sun,et al.  A mechanical model of actin stress fiber formation and substrate elasticity sensing in adherent cells , 2010, Proceedings of the National Academy of Sciences.

[114]  Margaret L. Gardel,et al.  Forcing cells into shape: the mechanics of actomyosin contractility , 2015, Nature Reviews Molecular Cell Biology.

[115]  Robert W Style,et al.  Traction force microscopy in physics and biology. , 2014, Soft matter.

[116]  David Swigon,et al.  Continuum Model of Collective Cell Migration in Wound Healing and Colony Expansion , 2022 .

[117]  Hannah G. Yevick,et al.  Perfect nematic order in confined monolayers of spindle-shaped cells. , 2014, Soft matter.

[118]  M. S. Cooper,et al.  Morphogenetic domains in the yolk syncytial layer of axiating zebrafish embryos , 2001, Developmental dynamics : an official publication of the American Association of Anatomists.

[119]  J. Fredberg,et al.  Cell migration driven by cooperative substrate deformation patterns. , 2010, Physical review letters.

[120]  William M. McFadden,et al.  Excitable RhoA dynamics drive pulsed contractions in the early C. elegans embryo , 2016, bioRxiv.

[121]  Paul Martin,et al.  Wound healing recapitulates morphogenesis in Drosophila embryos , 2002, Nature Cell Biology.