Collective multicellular patterns arising from cadherin-linked cytoskeletal domains

Abstract

I.In multicellular systems, adhesion complexes, such as those composed of E-cadherin and associated catenins, mechanically couple neighboring cells by directly linking their actin-based cytoskeletal assemblies. However, the mechanics of how forces are transmitted across these adhesions remains largely unstudied. Here, we introduce a biophysical model that explicitly couples adhesion complex dynamics to intracellular mechanics across cell boundaries. A cadherin dimer plus associated catenins connecting two cells is represented as a spring whose ends experience drag with respect to the moving actin cytoskeleton. The cytoskeleton is modeled as a contractile gel driven by myosin activity in its bulk and forces from adhesion on its boundaries. Our model captures this bidirectional coupling via a coarse-grained continuum framework and reveals a range of observed cell- and tissue-scale behaviors. These include global cell polarization of the multicellular collective, other polarization patterns and oscillatory dynamics, spontaneously formed actin rings within cells, and supracellular stress chains. Many of these features arise from modeling the direct mechanical coupling between cytoskeleton and adhesion. This model can be extended to other adhesion-cytoskeleton feedback systems and used to advance our understanding of multicellular tissue dynamics, particularly during development.