Adhesion-induced cortical flows pattern E-cadherin-mediated cell contacts

Curr Biol. 2024 Jan 8;34(1):171-182.e8. doi: 10.1016/j.cub.2023.11.067. Epub 2023 Dec 21.

Abstract

Metazoan development relies on the formation and remodeling of cell-cell contacts. Dynamic reorganization of adhesion receptors and the actomyosin cell cortex in space and time plays a central role in cell-cell contact formation and maturation. Nevertheless, how this process is mechanistically achieved when new contacts are formed remains unclear. Here, by building a biomimetic assay composed of progenitor cells adhering to supported lipid bilayers functionalized with E-cadherin ectodomains, we show that cortical F-actin flows, driven by the depletion of myosin-2 at the cell contact center, mediate the dynamic reorganization of adhesion receptors and cell cortex at the contact. E-cadherin-dependent downregulation of the small GTPase RhoA at the forming contact leads to both a depletion of myosin-2 and a decrease of F-actin at the contact center. At the contact rim, in contrast, myosin-2 becomes enriched by the retraction of bleb-like protrusions, resulting in a cortical tension gradient from the contact rim to its center. This tension gradient, in turn, triggers centrifugal F-actin flows, leading to further accumulation of F-actin at the contact rim and the progressive redistribution of E-cadherin from the contact center to the rim. Eventually, this combination of actomyosin downregulation and flows at the contact determines the characteristic molecular organization, with E-cadherin and F-actin accumulating at the contact rim, where they are needed to mechanically link the contractile cortices of the adhering cells.

Keywords: actomyosin; cadherin; cell adhesion; contact patterning; cortical flow; cortical tension; cytoskeleton; supported lipid bilayers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins* / metabolism
  • Actomyosin* / metabolism
  • Animals
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Adhesion / physiology
  • Cytoskeletal Proteins
  • Myosins

Substances

  • Actins
  • Actomyosin
  • Cadherins
  • Cytoskeletal Proteins
  • Myosins