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There is increasing interest in the analysis of biological tissue, itsorganization and its dynamics with the help of mathematical models. In theideal case emergent properties on the tissue scale can be derived from thecellular scale. However, this has been achieved in rare examples only, inparticular, when involving high-speed migration of cells. One major difficultyis the lack of a suitable multiscale simulation platform, which embedsreaction-diffusion of soluble substances, fast cell migration and mechanics,and, being of great importance in several tissue types, cell flow homeostasis.In this paper a step into this direction is presented by developing anagent-based mathematical model specifically designed to incorporate thesefeatures with special emphasis on high speed cell migration. Cells arerepresented as elastic spheres migrating on a substrate in lattice-free space.Their movement is regulated and guided by chemoattractants that can be derivedfrom the substrate. The diffusion of chemoattractants is considered to beslower than cell migration and, thus, to be far from equilibrium. Tissuehomeostasis is not achieved by the balance of growth and death but by a flowequilibrium of cells migrating in and out of the tissue under consideration. Inthis sense the number and the distribution of the cells in the tissue is aresult of the model and not part of the assumptions. For purpose ofdemonstration of the model properties and functioning, the model is applied toa prominent example of tissue in a cellular flow equilibrium, the secondarylymphoid tissue. The experimental data on cell speed distributions in thesetissues can be reproduced using reasonable mechanical parameters for thesimulated cell migration in dense tissue.Comment: 27 pages, 7 figures v2 major conceptual changes: stronger focus on  model architecture; new Fig 6, fitting of migration parameters; reduced Fig 7  (formerly Fig 6), shortened presentation of the application; equation (3)  provided in more detail; Fig 5 extende

Modeling emergent tissue organization involving high-speed migrating cells in a flow equilibrium