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

Area of Science:

• Cell Biology
• Biophysics
• Developmental Biology

Background:

• Cell-cell contact formation and remodeling are vital for metazoan development.
• The dynamic reorganization of adhesion receptors and the actomyosin cell cortex is central to cell-cell contact maturation.
• Mechanisms underlying these dynamic changes during new contact formation are not fully understood.

Purpose of the Study:

• To elucidate the mechanistic basis of dynamic cell cortex and adhesion receptor reorganization during the initial formation of cell-cell contacts.
• To investigate the role of F-actin flows and actomyosin dynamics in establishing mature cell-cell adhesions.

Main Methods:

• Development of a biomimetic assay using progenitor cells and supported lipid bilayers functionalized with E-cadherin ectodomains.
• Utilized live-cell imaging and biophysical techniques to observe and quantify molecular dynamics at forming cell contacts.
• Investigated the roles of E-cadherin, RhoA, myosin-2, and F-actin in regulating cortical organization and flows.

Main Results:

• Cortical F-actin flows, driven by myosin-2 depletion at the contact center, orchestrate the reorganization of adhesion receptors and the cell cortex.
• E-cadherin-mediated RhoA downregulation at the forming contact reduces myosin-2 and F-actin in the center.
• Myosin-2 enrichment at the contact rim, via bleb retraction, creates a tension gradient that drives centrifugal F-actin flows and E-cadherin redistribution to the rim.

Conclusions:

• The study reveals a novel mechanism for cell-cell contact maturation driven by actomyosin dynamics and F-actin flows.
• Centrifugal F-actin flows and E-cadherin accumulation at the contact rim are critical for mechanically linking the contractile cortices of adhering cells.
• This process establishes the characteristic molecular organization required for stable and functional cell-cell adhesion during development.