Biophysical Society Thematic Meeting| Aussois 2019

Biology and Physics Confront Cell-Cell Adhesion

Poster Abstracts

11-POS Board 11 LIGAND-INDEPENDENT EGFR ACTIVITY PROMOTES DYNAMIC JUNCTION REMODELLING Chaoyu Fu 1 ; Wilfried Engl 1 ; Michael Sheetz 1 ; Virgile Viasnoff 1 ; 1 Mechanobiology Institute, Singapore, Singapore A fundamental interrelationship between cell adhesion and Receptor Tyrosine Kinases (RTKs) governs the behavior of cells within tissues. Epidermal Growth Factor Receptor (EGFR), a well- studied RTK, and its activation by its ligand EGF are well known to weaken cell adhesion by promoting E-cadherin (E-cad) endocytosis or disrupting the association of E-cad to the actin cytoskeleton. However, the function of ligand-independent EGFR activity on E-cad adhesion remains largely elusive. This population of EGFR can be transiently activated by E-cad homophilic interactions in a ligand-independent manner during cell-cell contact formation. Here, we find a cooperativity effect between ligand-independent EGFR activity and E-cad adhesion, which promotes dynamic junction remodeling. We use a suspended cell doublet system to achieve the best control over junction formation dynamics and avoid any integrin signaling. We find during de novo junction formation, ligand-independent EGFR activity is triggered by E-cad interactions. This transiently activated EGFR regulates actomyosin cytoskeleton dynamics distal from the cell-cell contact as it slows down actin dynamics in the free cortex of doublets. By using junction formation time (τ) as a parameter to describe the speed of junction expansion in suspension, we find further junctions develop faster than the initial one and this priming effect of junction formation is regulated by ligand-independent EGFR activity. Since junction expansion is thought to be regulated by both actin polymerization and myosin contractility, we reasonably hypothesize that the slow actin dynamics in the free cortex of doublets affects the speed of further junction formation. To this end, we use several drugs targeting actomyosin cytoskeleton and measure their effect on junction formation speed. Consistently, we found slow actin dynamics and low cortical tension increase junction formation speed. Furthermore, we found ligand-independent EGFR activity promotes cell neighbor changing ability and collective cell migration, whereas it does not affect single cell motility.

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