Cell polarity triggered by cell-cell adhesion via E-cadherin

TLDR

Cell polarity is guided by extracellular cues and is essential for processes such as chemotaxis, mitosis, and wound healing; in scratch assays, wound-edge cells orient their centrosomes toward the wound via new cell‑ECM adhesions, whereas isolated cells lacking cell‑cell contacts fail to polarize, implying that asymmetry of cell‑cell adhesions from monolayer disruption may drive polarization. Micropatterned substrates were used to create asymmetric cell‑cell contacts in kidney epithelial cells, revealing that contact displaced the nucleus toward the contact site and induced centrosome reorientation and lamellipodial ruffling on the opposite side. When released from constraints, cells migrated away from the contact; disrupting E‑cadherin randomized nuclear position and lamellipodial ruffling and abolished wound‑induced reorientation but not migration speed, and polarity required actin and Cdc42 but not RhoA or Rac, demonstrating a novel role for cell‑cell adhesion in polarization with implications for wound healing and development.

Abstract

Cell polarity is orchestrated by numerous extracellular cues, and guides events such as chemotaxis, mitosis and wound healing. In scrape-wound assays of cell monolayers, wound-edge cells orient their centrosomes towards the wound, a process that appears to depend on the formation of new cell-extracellular-matrix adhesions as cells spread into the wound. In direct contrast to scrape-wounded cells, isolated cells without cell-cell contacts failed to polarize, suggesting that asymmetry of cell-cell adhesions resulting from monolayer disruption might contribute to polarization. By using micropatterned substrates to engineer such asymmetries in kidney epithelial cells, we found that cell-cell contact induced displacement of the nucleus towards the contact, and also caused centrosomal reorientation and lamellipodial ruffling to the distal side of the nucleus. Upon release from micropatterned constraints, cells exhibited directed migration away from the cell-cell contact. Disrupting E-cadherin engagement randomized nuclear position and lamellipodial ruffling in patterned cultures, and abrogated scrape-wound-induced cell reorientation, but not migration rate. Polarity that was induced by cell-cell contact required an intact actin cytoskeleton and Cdc42 activity, but not RhoA or Rac signaling. Together, these findings demonstrate a novel role for cell-cell adhesion in polarization, and have implications for wound healing and developmental patterning.