4.4 Article

A mathematical model for mesenchymal and chemosensitive cell dynamics

Journal

JOURNAL OF MATHEMATICAL BIOLOGY
Volume 64, Issue 1-2, Pages 361-401

Publisher

SPRINGER HEIDELBERG
DOI: 10.1007/s00285-011-0415-7

Keywords

Mesenchymal movement; Fibre network; Proteolysis; Chemotaxis; Metastasis; Mathematical modelling

Funding

  1. Deutsche Telekom Foundation

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The structure of an underlying tissue network has a strong impact on cell dynamics. If, in addition, cells alter the network by mechanical and chemical interactions, their movement is called mesenchymal. Important examples for mesenchymal movement include fibroblasts in wound healing and metastatic tumour cells. This paper is focused on the latter. Based on the anisotropic biphasic theory of Barocas and Tranquillo, which models a fibre network and interstitial solution as two-component fluid, a mathematical model for the interactions of cells with a fibre network is developed. A new description for fibre reorientation is given and orientation-dependent proteolysis is added to the model. With respect to cell dynamics, the equation, based on anisotropic diffusion, is extended by haptotaxis and chemotaxis. The chemoattractants are the solute network fragments, emerging from proteolysis, and the epidermal growth factor which may guide the cells to a blood vessel. Moreover the cell migration is impeded at either high or low network density. This new model enables us to study chemotactic cell migration in a complex fibre network and the consequential network deformation. Numerical simulations for the cell migration and network deformation are carried out in two space dimensions. Simulations of cell migration in underlying tissue networks visualise the impact of the network structure on cell dynamics. In a scenario for fibre reorientation between cell clusters good qualitative agreement with experimental results is achieved. The invasion speeds of cells in an aligned and an isotropic fibre network are compared.

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