Validity of the Cauchy-Born rule applied to discrete cellular-scale models of biological tissues.

The development of new models of biological tissues that consider cells in a discrete manner is becoming increasingly popular as an alternative to continuum methods based on partial differential equations, although formal relationships between the discrete and continuum frameworks remain to be established. For crystal mechanics, the discrete-to-continuum bridge is often made by assuming that local atom displacements can be mapped homogeneously from the mesoscale deformation gradient, an assumption known as the Cauchy-Born rule (CBR). Although the CBR does not hold exactly for noncrystalline materials, it may still be used as a first-order approximation for analytic calculations of effective stresses or strain energies. In this work, our goal is to investigate numerically the applicability of the CBR to two-dimensional cellular-scale models by assessing the mechanical behavior of model biological tissues, including crystalline (honeycomb) and noncrystalline reference states. The numerical procedure involves applying an affine deformation to the boundary cells and computing the quasistatic position of internal cells. The position of internal cells is then compared with the prediction of the CBR and an average deviation is calculated in the strain domain. For center-based cell models, we show that the CBR holds exactly when the deformation gradient is relatively small and the reference stress-free configuration is defined by a honeycomb lattice. We show further that the CBR may be used approximately when the reference state is perturbed from the honeycomb configuration. By contrast, for vertex-based cell models, a similar analysis reveals that the CBR does not provide a good representation of the tissue mechanics, even when the reference configuration is defined by a honeycomb lattice. The paper concludes with a discussion of the implications of these results for concurrent discrete and continuous modeling, adaptation of atom-to-continuum techniques to biological tissues, and model classification.

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

[2]  Hans Clevers,et al.  A Comprehensive Model of the Spatio-Temporal Stem Cell and Tissue Organisation in the Intestinal Crypt , 2011, PLoS Comput. Biol..

[3]  P. Cundall,et al.  A discrete numerical model for granular assemblies , 1979 .

[4]  François Graner,et al.  Yield drag in a two-dimensional foam flow around a circular obstacle: Effect of liquid fraction , 2006, The European physical journal. E, Soft matter.

[5]  S. Alexander,et al.  Amorphous solids: their structure, lattice dynamics and elasticity , 1998 .

[6]  Alexander G. Fletcher,et al.  Chaste: An Open Source C++ Library for Computational Physiology and Biology , 2013, PLoS Comput. Biol..

[7]  B. Gumbiner,et al.  Cell Adhesion: The Molecular Basis of Tissue Architecture and Morphogenesis , 1996, Cell.

[8]  Tatsuzo Nagai,et al.  A dynamic cell model for the formation of epithelial tissues , 2001 .

[9]  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.

[10]  L. Gibson Biomechanics of cellular solids. , 2005, Journal of biomechanics.

[11]  Gregory J. Wagner,et al.  Coupling of atomistic and continuum simulations using a bridging scale decomposition , 2003 .

[12]  Alexander G. Fletcher,et al.  Chaste: A test-driven approach to software development for biological modelling , 2009, Comput. Phys. Commun..

[13]  Hans G Othmer,et al.  Multi-scale models of cell and tissue dynamics , 2009, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

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

[15]  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.

[16]  J. Ericksen,et al.  On the Cauchy—Born Rule , 2008 .

[17]  M. Born,et al.  Dynamical Theory of Crystal Lattices , 1954 .

[18]  T. Newman,et al.  Modeling multicellular systems using subcellular elements. , 2005, Mathematical biosciences and engineering : MBE.

[19]  Richard B. Lehoucq,et al.  Peridynamics as an Upscaling of Molecular Dynamics , 2009, Multiscale Model. Simul..

[20]  Andreas Deutsch,et al.  Cellular Automaton Models of Tumor Development: a Critical Review , 2002, Adv. Complex Syst..

[21]  C. Broedersz,et al.  Nonlinear effective-medium theory of disordered spring networks. , 2011, Physical review. E, Statistical, nonlinear, and soft matter physics.

[22]  Pavel B. Bochev,et al.  On Atomistic-to-Continuum Coupling by Blending , 2008, Multiscale Model. Simul..

[23]  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.

[24]  Florian Theil,et al.  Validity and Failure of the Cauchy-Born Hypothesis in a Two-Dimensional Mass-Spring Lattice , 2002, J. Nonlinear Sci..

[25]  J. Barrat,et al.  Particle displacements in the elastic deformation of amorphous materials: Local fluctuations vs. non-affine field , 2006, cond-mat/0610518.

[26]  Ronald E. Miller,et al.  The Quasicontinuum Method: Overview, applications and current directions , 2002 .

[27]  I. Stakgold The Cauchy relations in a molecular theory of elasticity , 1950 .

[28]  H. Othmer,et al.  A HYBRID MODEL FOR TUMOR SPHEROID GROWTH IN VITRO I: THEORETICAL DEVELOPMENT AND EARLY RESULTS , 2007 .

[29]  M. Loeffler,et al.  Modeling the effect of deregulated proliferation and apoptosis on the growth dynamics of epithelial cell populations in vitro. , 2005, Biophysical journal.

[30]  D. Reinelt,et al.  Structure of random monodisperse foam. , 2003, Physical review. E, Statistical, nonlinear, and soft matter physics.

[31]  C. Broedersz,et al.  Criticality and isostaticity in fibre networks , 2010, 1011.6535.

[32]  C. Broedersz,et al.  Filament-length-controlled elasticity in 3D fiber networks. , 2011, Physical review letters.

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

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

[35]  Mark S. Shephard,et al.  Concurrent AtC coupling based on a blend of the continuum stress and the atomistic force , 2007 .

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

[37]  M. Bodnar,et al.  An integro-differential equation arising as a limit of individual cell-based models , 2006 .

[38]  P. Maini,et al.  Towards whole-organ modelling of tumour growth. , 2004, Progress in biophysics and molecular biology.

[39]  Min Zhou,et al.  A new look at the atomic level virial stress: on continuum-molecular system equivalence , 2003, Proceedings of the Royal Society of London. Series A: Mathematical, Physical and Engineering Sciences.

[40]  Tatsuzo Nagai,et al.  A three-dimensional vertex dynamics cell model of space-filling polyhedra simulating cell behavior in a cell aggregate. , 2004, Journal of theoretical biology.

[41]  Davide Carlo Ambrosi,et al.  Active Stress vs. Active Strain in Mechanobiology: Constitutive Issues , 2012 .

[42]  C. Brangwynne,et al.  Mechanical Response of Cytoskeletal Networks , 2008 .

[43]  Mohammad Taghi Kazemi,et al.  Stability and size-dependency of Cauchy–Born hypothesis in three-dimensional applications , 2009 .

[44]  M. Ortiz,et al.  An adaptive finite element approach to atomic-scale mechanics—the quasicontinuum method , 1997, cond-mat/9710027.