Bistable front dynamics in a contractile medium: Travelling wave fronts and cortical advection define stable zones of RhoA signaling at epithelial adherens junctions

PLoS Comput Biol. 2017 Mar 8;13(3):e1005411. doi: 10.1371/journal.pcbi.1005411. eCollection 2017 Mar.

Abstract

Mechanical coherence of cell layers is essential for epithelia to function as tissue barriers and to control active tissue dynamics during morphogenesis. RhoA signaling at adherens junctions plays a key role in this process by coupling cadherin-based cell-cell adhesion together with actomyosin contractility. Here we propose and analyze a mathematical model representing core interactions involved in the spatial localization of junctional RhoA signaling. We demonstrate how the interplay between biochemical signaling through positive feedback, combined with diffusion on the cell membrane and mechanical forces generated in the cortex, can determine the spatial distribution of RhoA signaling at cell-cell junctions. This dynamical mechanism relies on the balance between a propagating bistable signal that is opposed by an advective flow generated by an actomyosin stress gradient. Experimental observations on the behavior of the system when contractility is inhibited are in qualitative agreement with the predictions of the model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actomyosin / chemistry
  • Actomyosin / physiology*
  • Adherens Junctions / chemistry
  • Adherens Junctions / physiology*
  • Animals
  • Computer Simulation
  • Epithelial Cells / chemistry
  • Epithelial Cells / physiology*
  • Humans
  • Mechanotransduction, Cellular / physiology*
  • Models, Biological
  • Molecular Motor Proteins / chemistry
  • Molecular Motor Proteins / physiology
  • Muscle Contraction / physiology*
  • Stress, Mechanical
  • rhoA GTP-Binding Protein / chemistry
  • rhoA GTP-Binding Protein / physiology*

Substances

  • Molecular Motor Proteins
  • Actomyosin
  • rhoA GTP-Binding Protein