Cell traction models for generating pattern and form in morphogenesis
bifurcationcell migrationcell motioncell traction modelscell-matrix interactionchondrogenesislogistic growth modelmesenchymal cell morphogenesismitosismodel simulationpattern formation
Biomechanical solid mechanics (74L15) Physiological flows (76Z05) General biology and biomathematics (92B05) Physiological, cellular and medical topics (92Cxx) Lyapunov and other classical stabilities (Lagrange, Poisson, (L^p, l^p), etc.) in control theory (93D05) Stabilization of systems by feedback (93D15)
A model for mesenchymal cell morphogenesis is presented which is based only on physical properties of the process of cell migration within the elastic medium of extracellular matrix (ECM). The motile cells generate traction forces which deform the ECM. These cell-produced deformations take effect back to the cell motions in that spatially organized cell aggregations can spontaneously be formed. The mathematical model consists of equations governing the cell density, expressing the mechanical balance of forces between the cell tractions and the ECM, and of the conservation equation for the matrix material. The first equation contains a random dispersial term (consisting of 2 components representing a short range random motion and a long range interaction), a haptotactic flux term, a convection term which represents the passive movement of cells riding on the matrix, and a term of mitosis for which a logistic growth model is assumed. For the cell-matrix interaction the usual expression for the viscoelastic stress tensor is modified to account for the fibrous nature of the ECM, the effects of external elastic forces on the system, and the contribution of cell traction to the elastic properties. In the matrix density equation the secretion rate of matrix material by the cells is neglected. By a combination of linear stability analysis of the model equations and numerical simulation some of the model properties are worked out. The stability for various special cases (for instance a model simplification of no long range cell interactions as well as no haptotaxis and no mitosis, or no viscous damping of cell contractions) is studied using the cell traction parameter as the bifurcation parameter. It is shown that a variety of spatial patterns may be generated by the model equations. The model is applied to pattern forming processes where motile mesenchymal cell populations aggregate into geometrically organized spatial patterns, such as the formation of feather, scale or teeth primordia, cartilage condensation patterns which presage bone formation in limb development, and melanocyte density patterns which form animal coat patterns. Also certain aspects of the wound healing process may be reflected by the model.
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