A continuum approximation to an off-lattice individual-cell based model of cell migration and adhesion.

Cell-cell adhesion plays a key role in the collective migration of cells and in determining correlations in the relative cell positions and velocities. Recently, it was demonstrated that off-lattice individual cell based models (IBMs) can accurately capture the correlations observed experimentally in a migrating cell population. However, IBMs are often computationally expensive and difficult to analyse mathematically. Traditional continuum-based models, in contrast, are amenable to mathematical analysis and are computationally less demanding, but typically correspond to a mean-field approximation of cell migration and so ignore cell-cell correlations. In this work, we address this problem by using an off-lattice IBM to derive a continuum approximation which does take into account correlations. We furthermore show that a mean-field approximation of the off-lattice IBM leads to a single partial integro-differential equation of the same form as proposed by Sherratt and co-workers to model cell adhesion. The latter is found to be only effective at approximating the ensemble averaged cell number density when mechanical interactions between cells are weak. In contrast, the predictions of our novel continuum model for the time-evolution of the ensemble cell number density distribution and of the density-density correlation function are in close agreement with those obtained from the IBM for a wide range of mechanical interaction strengths. In particular, we observe 'front-like' propagation of cells in simulations using both our IBM and our continuum model, but not in the continuum model simulations obtained using the mean-field approximation.

[1]  Massimo Fornasier,et al.  Particle, kinetic, and hydrodynamic models of swarming , 2010 .

[2]  Gary R. Mirams,et al.  A hybrid approach to multi-scale modelling of cancer , 2010, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[3]  M. Alber,et al.  Macroscopic model of self-propelled bacteria swarming with regular reversals. , 2011, Physical review. E, Statistical, nonlinear, and soft matter physics.

[4]  P. Rørth,et al.  Collective cell migration. , 2009, Annual review of cell and developmental biology.

[5]  K. Kendall,et al.  Surface energy and the contact of elastic solids , 1971, Proceedings of the Royal Society of London. A. Mathematical and Physical Sciences.

[6]  James D. Murray,et al.  Spatial models and biomedical applications , 2003 .

[7]  Martin Burger,et al.  Large time behavior of nonlocal aggregation models with nonlinear diffusion , 2008, Networks Heterog. Media.

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

[9]  J. Linnett,et al.  Quantum mechanics , 1975, Nature.

[10]  Andreas Deutsch,et al.  Cellular Automaton Modeling of Biological Pattern Formation - Characterization, Applications, and Analysis , 2005, Modeling and simulation in science, engineering and technology.

[11]  Kevin J Painter,et al.  The impact of adhesion on cellular invasion processes in cancer and development. , 2010, Journal of theoretical biology.

[12]  Torbjörn Lundh,et al.  Cellular Automaton Modeling of Biological Pattern Formation: Characterization, Applications, and Analysis Authors: Andreas Deutsch and Sabine Dormann, Birkhäuser, 2005, XXVI, 334 p., 131 illus., Hardcover. ISBN:0-8176-4281-1, List Price: $89.95 , 2007, Genetic Programming and Evolvable Machines.

[13]  E. Platen An introduction to numerical methods for stochastic differential equations , 1999, Acta Numerica.

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

[15]  M. Loeffler,et al.  Cell migration and organization in the intestinal crypt using a lattice‐free model , 2001, Cell proliferation.

[16]  Matthew J Simpson,et al.  Mean-field descriptions of collective migration with strong adhesion. , 2012, Physical review. E, Statistical, nonlinear, and soft matter physics.

[17]  P. Friedl,et al.  Tumour-cell invasion and migration: diversity and escape mechanisms , 2003, Nature Reviews Cancer.

[18]  Matthew J Simpson,et al.  Migration of breast cancer cells: understanding the roles of volume exclusion and cell-to-cell adhesion. , 2010, Physical review. E, Statistical, nonlinear, and soft matter physics.

[19]  Peter T. Cummings,et al.  An off-lattice hybrid discrete-continuum model of tumor growth and invasion. , 2010, Biophysical journal.

[20]  J. W. Thomas Numerical Partial Differential Equations: Finite Difference Methods , 1995 .

[21]  Mark Alber,et al.  Macroscopic dynamics of biological cells interacting via chemotaxis and direct contact. , 2008, Physical review. E, Statistical, nonlinear, and soft matter physics.

[22]  Chuan Xue,et al.  The Mathematical Analysis of Biological Aggregation and Dispersal: Progress, Problems and Perspectives , 2013 .

[23]  A. Singer,et al.  Maximum entropy formulation of the Kirkwood superposition approximation. , 2004, The Journal of chemical physics.

[24]  G. Verghese,et al.  Mass fluctuation kinetics: capturing stochastic effects in systems of chemical reactions through coupled mean-variance computations. , 2007, The Journal of chemical physics.

[25]  Christopher R. Sweet,et al.  Modelling platelet–blood flow interaction using the subcellular element Langevin method , 2011, Journal of The Royal Society Interface.

[26]  J. Schwartz,et al.  Theory of Self-Reproducing Automata , 1967 .

[27]  S. Schnell,et al.  A systematic investigation of the rate laws valid in intracellular environments. , 2006, Biophysical chemistry.

[28]  Philip K Maini,et al.  Classifying general nonlinear force laws in cell-based models via the continuum limit. , 2012, Physical review. E, Statistical, nonlinear, and soft matter physics.

[29]  K. Painter,et al.  A continuum approach to modelling cell-cell adhesion. , 2006, Journal of theoretical biology.

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

[31]  Ramon Grima,et al.  A study of the accuracy of moment-closure approximations for stochastic chemical kinetics. , 2012, The Journal of chemical physics.

[32]  Vincent Hakim,et al.  Collective Cell Motion in an Epithelial Sheet Can Be Quantitatively Described by a Stochastic Interacting Particle Model , 2013, PLoS Comput. Biol..

[33]  L. Segel,et al.  Model for chemotaxis. , 1971, Journal of theoretical biology.

[34]  Glazier,et al.  Simulation of the differential adhesion driven rearrangement of biological cells. , 1993, Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics.

[35]  G Mirams,et al.  A computational study of discrete mechanical tissue models , 2009, Physical biology.

[36]  Philip K Maini,et al.  From a discrete to a continuum model of cell dynamics in one dimension. , 2009, Physical review. E, Statistical, nonlinear, and soft matter physics.

[37]  M. Manning,et al.  Knowing the Boundaries: Extending the Differential Adhesion Hypothesis in Embryonic Cell Sorting , 2012, Science.

[38]  C. Gardiner Handbook of Stochastic Methods , 1983 .

[39]  R. Grima,et al.  Many-body theory of chemotactic cell-cell interactions. , 2004, Physical review. E, Statistical, nonlinear, and soft matter physics.

[40]  Thomas Laurent,et al.  Local and Global Existence for an Aggregation Equation , 2007 .

[41]  조준학,et al.  Growth of human bronchial epithelial cells at an air-liquid interface alters the response to particle exposure , 2013, Particle and Fibre Toxicology.

[42]  H. Othmer,et al.  A model for individual and collective cell movement in Dictyostelium discoideum. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[43]  H. Berg Random Walks in Biology , 2018 .

[44]  T. J. Newman Modeling multi-cellular systems using sub-cellular elements , 2005 .

[45]  Marek Bodnar,et al.  Derivation of macroscopic equations for individual cell‐based models: a formal approach , 2005 .

[46]  C. Gillespie Moment-closure approximations for mass-action models. , 2009, IET systems biology.

[47]  T. Vicsek,et al.  Collective Motion , 1999, physics/9902023.

[48]  W. R. Young,et al.  Reproductive pair correlations and the clustering of organisms , 2001, Nature.

[49]  D. L. Sean McElwain,et al.  Travelling waves in a wound healing assay , 2004, Appl. Math. Lett..

[50]  P. Mattila,et al.  Filopodia: molecular architecture and cellular functions , 2008, Nature Reviews Molecular Cell Biology.

[51]  Andrea L. Bertozzi,et al.  Finite-time blow-up of L∞-weak solutions of an aggregation equation , 2010 .

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

[53]  José C. M. Mombach SIMULATION OF EMBRYONIC CELL SELF-ORGANIZATION : A STUDY OF AGGREGATES WITH DIFFERENT CONCENTRATIONS OF CELL TYPES , 1999 .

[54]  Christophe Deroulers,et al.  Modeling tumor cell migration: From microscopic to macroscopic models. , 2008, Physical review. E, Statistical, nonlinear, and soft matter physics.

[55]  J. McCaskill,et al.  Monte Carlo approach to tissue-cell populations. , 1995, Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics.

[56]  A. Mogilner,et al.  Mathematical Biology Mutual Interactions, Potentials, and Individual Distance in a Social Aggregation , 2003 .

[57]  J. Sherratt,et al.  Intercellular adhesion and cancer invasion: a discrete simulation using the extended Potts model. , 2002, Journal of theoretical biology.

[58]  Matthew J Simpson,et al.  Corrected mean-field models for spatially dependent advection-diffusion-reaction phenomena. , 2011, Physical review. E, Statistical, nonlinear, and soft matter physics.

[59]  Helen M. Byrne,et al.  Continuum approximations of individual-based models for epithelial monolayers. , 2010, Mathematical medicine and biology : a journal of the IMA.

[60]  J. Kirkwood Statistical Mechanics of Fluid Mixtures , 1935 .

[61]  A. Messiah Quantum Mechanics , 1961 .

[62]  Kevin J Painter,et al.  Adding Adhesion to a Chemical Signaling Model for Somite Formation , 2009, Bulletin of mathematical biology.

[63]  T. Vicsek,et al.  Phase transition in the collective migration of tissue cells: experiment and model. , 2006, Physical review. E, Statistical, nonlinear, and soft matter physics.

[64]  R. Grima Multiscale modeling of biological pattern formation. , 2008, Current topics in developmental biology.

[65]  D. Drasdo,et al.  A single-cell-based model of tumor growth in vitro: monolayers and spheroids , 2005, Physical biology.

[66]  J. M. Sancho,et al.  Noise in spatially extended systems , 1999 .

[67]  Matthew J. Simpson,et al.  A model for mesoscale patterns in motile populations , 2010 .

[68]  K. Painter,et al.  Cellular automata and integrodifferential equation models for cell renewal in mosaic tissues , 2010, Journal of The Royal Society Interface.

[69]  H M Byrne,et al.  Non-local models for the formation of hepatocyte-stellate cell aggregates. , 2010, Journal of theoretical biology.

[70]  Mark Alber,et al.  Continuous macroscopic limit of a discrete stochastic model for interaction of living cells. , 2007, Physical review letters.

[71]  G. M.,et al.  A Treatise on the Mathematical Theory of Elasticity , 1906, Nature.

[72]  E. Tadmor,et al.  From particle to kinetic and hydrodynamic descriptions of flocking , 2008, 0806.2182.

[73]  Kevin J Painter,et al.  From a discrete to a continuous model of biological cell movement. , 2004, Physical review. E, Statistical, nonlinear, and soft matter physics.

[74]  R. Beddington,et al.  Active cell migration drives the unilateral movements of the anterior visceral endoderm , 2004, Development.

[75]  Leonard M. Sander,et al.  Pattern formation of glioma cells: Effects of adhesion , 2007 .

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

[77]  H. Chaté,et al.  Modeling collective motion: variations on the Vicsek model , 2008 .

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

[79]  P. Friedl,et al.  Collective cell migration in morphogenesis and cancer. , 2004, The International journal of developmental biology.

[80]  Accurate discretization of advection-diffusion equations. , 2004, Physical review. E, Statistical, nonlinear, and soft matter physics.

[81]  Andrea L. Bertozzi,et al.  Finite-Time Blow-up of Solutions of an Aggregation Equation in Rn , 2007 .

[82]  Felipe Cucker,et al.  Emergent Behavior in Flocks , 2007, IEEE Transactions on Automatic Control.

[83]  Jonathan A. Sherratt,et al.  Models of epidermal wound healing , 1990, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[84]  T. Newman,et al.  Modeling cell rheology with the Subcellular Element Model , 2008, Physical biology.