The Journal of Biological Physics and Chemistry

Cellular networks morphogenesis induced by mechanically stressed microenvironments

Philippe Tracqui, Patrick Namy and Jacques Ohayon

While the Turing reaction-diffusion pre-pattern theory of morphogenesis has been successfully applied to explain the emergence of morphogenetic patterns in different experimental situations, physical properties of extracellular matrices (ECM) are now emerging as unavoidable actors of morphogenetic scenarios observed from subcellular to tissue levels. ECM display adhesive ligand gradients important for anchorage-dependent cells’ motility and for the resulting directional cell locomotion coupled to cellular traction forces. We review here formal descriptions of these cell-ECM interactions as a basis for understanding how strain propagation within the ECM may define morphogenetic fields which trigger cell aggregation processes. We first consider the generic morphogenetic properties emerging in planar cell cultures when cell migration is guided by physico-chemical interactions at the cell-substrate interface. We then illustrate how the dynamical instabilities induced by the balance between cellular forces and ECM compliance generate the different cellular network morphologies observed when endothelial cells are cultured on biogels. Considering more specifically experiments conducted on fibrin gels, we show that experimental bell-shaped angiogenic index curves can be explained by spatio-temporal evolution of the mechanical stress fields within the biogel. We discuss how these results could be included in a multi-scale modelling of the angiogenesis signalling network

Keywords: cellular haptotaxis, cellular traction, extracellular matrix rheology, in vitro angiogenesis, mechanical signalling, pattern formation