Generation of fate patterns via intercellular forces

Abstract

Studies of fate patterning during development typically emphasize cell-cell communication via diffusible signals. Recent experiments on monolayer stem cell colonies, however, suggest that mechanical forces between cells may also play a role. These findings inspire a model of mechanical patterning: fate affects cell contractility, and pressure in the cell layer biases fate. Cells at the colony boundary, more contractile than cells at the center, seed a pattern that propagates via force transmission. In agreement with previous observations, our model implies that the width of the outer fate domain depends only weakly on colony diameter. We further predict and confirm experimentally that this same width varies non-monotonically with substrate stiffness. This finding supports the idea that mechanical stress can mediate patterning in a manner similar to a morphogen; we argue that a similar dependence on substrate stiffness can be achieved by a chemical signal only if strong constraints on the signaling pathways mechanobiology are met.