Mechanical signalling and angiogenesis. The integration of cell-extracellular matrix couplings

In vitro angiogenesis assays have shown that the couplings between fibrin g el and cell traction forces trigger biogel pre-patterning, consisting in th e formation of lacunae which evolve toward capillary-like structures (CLS) networks. Depending on the experimental conditions (number of seeded cells, gel elasticity...), this pre-patterning can be enhanced or inhibited. A th eoretical model based on a description of the cell-biogel biochemical and m echanical interactions is proposed as a basis for understanding how integra ting these interactions can lead to the pre-patterning of the biogel. We sh owed that the critical parameter values corresponding to the bifurcation of the model solutions correspond to threshold values of the experimental var iables. Furthermore, simulations of the mechanocellular model give rise to dynamic remodelling patterns of the biogel which are in good agreement both with the lacunae morphologies and with the time and space scales derived f rom the in vitro angiogenesis assays. Special attention has been paid in th e simulations to cell proteolytic activity and to the amplitude of cell tra ction forces. We finally discussed how modelling guided experiments can be inferred from these results. (C) 2000 Academie des sciences/Editions scient ifiques et medicales Elsevier SAS.