Mean-field approach to evolving spatial networks, with an application to osteocyte network formation.

We consider evolving networks in which each node can have various associated properties (a state) in addition to those that arise from network structure. For example, each node can have a spatial location and a velocity, or it can have some more abstract internal property that describes something like a social trait. Edges between nodes are created and destroyed, and new nodes enter the system. We introduce a "local state degree distribution" (LSDD) as the degree distribution at a particular point in state space. We then make a mean-field assumption and thereby derive an integro-partial differential equation that is satisfied by the LSDD. We perform numerical experiments and find good agreement between solutions of the integro-differential equation and the LSDD from stochastic simulations of the full model. To illustrate our theory, we apply it to a simple model for osteocyte network formation within bones, with a view to understanding changes that may take place during cancer. Our results suggest that increased rates of differentiation lead to higher densities of osteocytes, but with a smaller number of dendrites. To help provide biological context, we also include an introduction to osteocytes, the formation of osteocyte networks, and the role of osteocytes in bone metastasis.

[1]  B. Gillham,et al.  Number , 2018, A Grammar of Mursi.

[2]  R. Illner,et al.  A derivation of the BBGKY-hierarchy for hard sphere particle systems , 1987 .

[3]  K. Ackermann,et al.  Metastases and multiple myeloma generate distinct transcriptional footprints in osteocytes in vivo , 2008, The Journal of pathology.

[4]  Laurent Desvillettes,et al.  From Reactive Boltzmann Equations to Reaction–Diffusion Systems , 2006 .

[5]  R. Bacabac,et al.  The Osteocyte as an Orchestrator of Bone Remodeling: An Engineer’s Perspective , 2014, Clinical Reviews in Bone and Mineral Metabolism.

[6]  Sang Hoon Lee,et al.  Mesoscale analyses of fungal networks as an approach for quantifying phenotypic traits , 2014, bioRxiv.

[7]  Marc Barthelemy,et al.  Spatial Networks , 2010, Encyclopedia of Social Network Analysis and Mining.

[8]  Thilo Gross,et al.  Adaptive coevolutionary networks: a review , 2007, Journal of The Royal Society Interface.

[9]  M. Archetti,et al.  Evolutionary game theory of growth factor production: implications for tumour heterogeneity and resistance to therapies , 2013, British Journal of Cancer.

[10]  G. Szabó,et al.  Evolutionary games on graphs , 2006, cond-mat/0607344.

[11]  Jason M. Graham,et al.  The Role of Osteocytes in Targeted Bone Remodeling: A Mathematical Model , 2012, PloS one.

[12]  Marc D. Ryser,et al.  Osteoprotegerin in Bone Metastases: Mathematical Solution to the Puzzle , 2012, PLoS Comput. Biol..

[13]  R. Pastor-Satorras,et al.  Class of correlated random networks with hidden variables. , 2003, Physical review. E, Statistical, nonlinear, and soft matter physics.

[14]  A. Rbnyi ON THE EVOLUTION OF RANDOM GRAPHS , 2001 .

[15]  S. Jonathan Chapman,et al.  From Brownian Dynamics to Markov Chain: An Ion Channel Example , 2012, SIAM J. Appl. Math..

[16]  C. Logothetis,et al.  Osteoblasts in prostate cancer metastasis to bone , 2005, Nature Reviews Cancer.

[17]  S. Redner,et al.  A Kinetic View of Statistical Physics , 2010 .

[18]  G. Marotti,et al.  Number, size and arrangement of osteoblasts in osteons at different stages of formation , 1975, Calcified Tissue Research.

[19]  B. Enquist,et al.  Venation networks and the origin of the leaf economics spectrum. , 2011, Ecology letters.

[20]  D. Gillespie Exact Stochastic Simulation of Coupled Chemical Reactions , 1977 .

[21]  H. Ohtsuki,et al.  A simple rule for the evolution of cooperation on graphs and social networks , 2006, Nature.

[22]  Marc D. Ryser,et al.  The Cellular Dynamics of Bone Remodeling: A Mathematical Model , 2010, SIAM J. Appl. Math..

[23]  Hubert Vesselle,et al.  Phenotypic heterogeneity of end-stage prostate carcinoma metastatic to bone. , 2003, Human pathology.

[24]  P. Maini,et al.  Growth-induced mass flows in fungal networks , 2010, Proceedings of the Royal Society B: Biological Sciences.

[25]  Peter Markowich,et al.  Mathematical Analysis of a PDE System for Biological Network Formation , 2014, 1405.0857.

[26]  J M Smith,et al.  Evolution and the theory of games , 1976 .

[27]  Joel Nishimura,et al.  Configuring Random Graph Models with Fixed Degree Sequences , 2016, SIAM Rev..

[28]  Peter Pivonka,et al.  Mathematical modeling in bone biology: from intracellular signaling to tissue mechanics. , 2010, Bone.

[29]  Desmond J. Higham,et al.  An Algorithmic Introduction to Numerical Simulation of Stochastic Differential Equations , 2001, SIAM Rev..

[30]  T. Takano-Yamamoto,et al.  A three-dimensional distribution of osteocyte processes revealed by the combination of confocal laser scanning microscopy and differential interference contrast microscopy. , 2001, Bone.

[31]  Philip Kollmannsberger,et al.  Architecture of the osteocyte network correlates with bone material quality , 2013, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[32]  J. Foekens,et al.  Selection of Bone Metastasis Seeds by Mesenchymal Signals in the Primary Tumor Stroma , 2013, Cell.

[33]  Yanping Lin,et al.  On the $L^2$-moment closure of transport equations: The Cattaneo approximation , 2004 .

[34]  R. Bataille,et al.  Osteoblast stimulation in multiple myeloma lacking lytic bone lesions , 1990, British journal of haematology.

[35]  Pierre Degond,et al.  Particle Interactions Mediated by Dynamical Networks: Assessment of Macroscopic Descriptions , 2017, Journal of Nonlinear Science.

[36]  Maria Bruna,et al.  Excluded-volume effects in the diffusion of hard spheres. , 2010, Physical review. E, Statistical, nonlinear, and soft matter physics.

[37]  D. Cooper,et al.  Normal variation in cortical osteocyte lacunar parameters in healthy young males , 2014, Journal of anatomy.

[38]  H. Othmer,et al.  Models of dispersal in biological systems , 1988, Journal of mathematical biology.

[39]  Garry Robins,et al.  A spatial model for social networks , 2006 .

[40]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[41]  A. Anderson,et al.  Hybrid models of tumor growth , 2011, Wiley interdisciplinary reviews. Systems biology and medicine.

[42]  David Basanta,et al.  An integrated computational model of the bone microenvironment in bone-metastatic prostate cancer. , 2014, Cancer research.

[43]  Marián Boguñá,et al.  Emergence of Soft Communities from Geometric Preferential Attachment , 2015, Scientific Reports.

[44]  A. Piattelli,et al.  Osteocyte density in the peri-implant bone of implants retrieved after different time periods (4 weeks to 27 years). , 2014, Journal of biomedical materials research. Part B, Applied biomaterials.

[45]  T. Yamashiro,et al.  In situ imaging of the autonomous intracellular Ca(2+) oscillations of osteoblasts and osteocytes in bone. , 2012, Bone.

[46]  M. Barthelemy,et al.  How congestion shapes cities: from mobility patterns to scaling , 2014, Scientific Reports.

[47]  J. Carrillo,et al.  Double milling in self-propelled swarms from kinetic theory , 2009 .

[48]  N. Sims,et al.  Quantifying the osteocyte network in the human skeleton. , 2015, Bone.

[49]  B. Hall,et al.  Buried alive: How osteoblasts become osteocytes , 2006, Developmental dynamics : an official publication of the American Association of Anatomists.

[50]  R. Weinstein,et al.  Osteocyte-derived RANKL is a critical mediator of the increased bone resorption caused by dietary calcium deficiency. , 2014, Bone.

[51]  Isabelle Gallagher,et al.  From Newton to Boltzmann: Hard Spheres and Short-range Potentials , 2012, 1208.5753.

[52]  Aaas News,et al.  Book Reviews , 1893, Buffalo Medical and Surgical Journal.

[53]  Alex Arenas,et al.  Emergence of clustering, correlations, and communities in a social network model , 2003 .

[54]  Gourab Ghoshal,et al.  Exact solutions for models of evolving networks with addition and deletion of nodes. , 2006, Physical review. E, Statistical, nonlinear, and soft matter physics.

[55]  Mark Newman,et al.  Networks: An Introduction , 2010 .

[56]  R. Satcher,et al.  BMP4 promotes prostate tumor growth in bone through osteogenesis. , 2011, Cancer research.

[57]  M. K. Knothe Tate,et al.  The osteocyte. , 2004, The international journal of biochemistry & cell biology.

[58]  Dmitri Krioukov,et al.  Duality between equilibrium and growing networks. , 2013, Physical review. E, Statistical, nonlinear, and soft matter physics.

[59]  J. Klafter,et al.  The random walk's guide to anomalous diffusion: a fractional dynamics approach , 2000 .

[60]  Mason A. Porter,et al.  Mesoscale Analyses of Fungal Networks , 2014 .

[61]  Dan Hu,et al.  Adaptation and optimization of biological transport networks. , 2013, Physical review letters.

[62]  P. Buenzli Osteocytes as a record of bone formation dynamics: a mathematical model of osteocyte generation in bone matrix. , 2014, Journal of theoretical biology.

[63]  S Redner,et al.  Degree distributions of growing networks. , 2001, Physical review letters.

[64]  Teruko Takano-Yamamoto,et al.  Three-dimensional reconstruction of chick calvarial osteocytes and their cell processes using confocal microscopy. , 2005, Bone.

[65]  Nilima Nigam,et al.  Mathematical Modeling of Spatio‐Temporal Dynamics of a Single Bone Multicellular Unit , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[66]  J. Dall,et al.  Random geometric graphs. , 2002, Physical review. E, Statistical, nonlinear, and soft matter physics.

[67]  Mason A. Porter,et al.  Multilayer networks , 2013, J. Complex Networks.

[68]  J. Peacock Two-dimensional goodness-of-fit testing in astronomy , 1983 .

[69]  R. Weinstein,et al.  Osteocyte apoptosis. , 2013, Bone.

[70]  D. E. Matthews Evolution and the Theory of Games , 1977 .

[71]  T. Hillen ON THE L 2 -MOMENT CLOSURE OF TRANSPORT EQUATIONS: THE GENERAL CASE , 2005 .

[72]  Adam Moroz,et al.  On allosteric control model of bone turnover cycle containing osteocyte regulation loop , 2007, Biosyst..

[73]  O. Kennedy,et al.  Osteocyte apoptosis is required for production of osteoclastogenic signals following bone fatigue in vivo. , 2014, Bone.

[74]  Marc Barthelemy,et al.  Anatomy and efficiency of urban multimodal mobility , 2014, Scientific Reports.

[75]  Christian Kuehn,et al.  Moment Closure—A Brief Review , 2015, 1505.02190.

[76]  R K Jain,et al.  Determinants of tumor blood flow: a review. , 1988, Cancer research.

[77]  Alexander G Robling,et al.  Biomechanical and molecular regulation of bone remodeling. , 2006, Annual review of biomedical engineering.

[78]  C. Cercignani The Boltzmann equation and its applications , 1988 .

[79]  G. Livshits,et al.  Osteocyte control of bone remodeling: is sclerostin a key molecular coordinator of the balanced bone resorption–formation cycles? , 2014, Osteoporosis International.

[80]  R. Akhurst,et al.  Complexities of TGF-β Targeted Cancer Therapy , 2012, International journal of biological sciences.

[81]  Geoff Smith,et al.  Phenomenological model of bone remodeling cycle containing osteocyte regulation loop. , 2006, Bio Systems.

[82]  F. De Carlo,et al.  Bimodal distribution of osteocyte lacunar size in the human femoral cortex as revealed by micro-CT. , 2010, Bone.

[83]  R. Durrett,et al.  The Importance of Being Discrete (and Spatial) , 1994 .

[84]  S. Redner,et al.  Organization of growing random networks. , 2000, Physical review. E, Statistical, nonlinear, and soft matter physics.

[85]  L. Bonewald,et al.  Dynamics of the transition from osteoblast to osteocyte , 2010, Annals of the New York Academy of Sciences.

[86]  Helen M. Byrne,et al.  Continuum Modelling of In Vitro Tissue Engineering: A Review , 2012 .

[87]  Yoshihito Ishihara,et al.  The Three-Dimensional Morphometry and Cell–Cell Communication of the Osteocyte Network in Chick and Mouse Embryonic Calvaria , 2011, Calcified Tissue International.

[88]  L. Hébert-Dufresne,et al.  Adaptive networks: Coevolution of disease and topology. , 2010, Physical review. E, Statistical, nonlinear, and soft matter physics.

[89]  Lorenzo Pareschi,et al.  Modeling and Computational Methods for Kinetic Equations , 2012 .

[90]  P. Erdos,et al.  On the evolution of random graphs , 1984 .

[91]  David W. Smith,et al.  Bone refilling in cortical basic multicellular units: insights into tetracycline double labelling from a computational model , 2012, Biomechanics and modeling in mechanobiology.