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 pathway’s mechanobiology are met.

A contraction-reaction-diffusion model for circular pattern formation in embryogenesis

“…For the pattern formation during early embryogenesis, experimental studies reveal that mechanical cues could also play a dominating role in dictating the distribution of signaling molecules 21,24,35 . Based on these findings, quite a number of mechanical-coupling reaction-diffusion models have been proposed to study the pattern formation in stem cell differentiation during early embryogenesis 19,[36][37][38][39] . In these studies, the cellular tissues have been modelled as homogeneous single-phase elastic solids, where the morphogens/signaling molecules can diffuse across the whole piece of the material.…”