E-cadherin mediated lateral interactions between neighbor cells necessary for collective migration

• Published in: Journal of biomechanics 2018-04, Vol.71, p.159-166
• Main Authors: Suffoletto, Kevin, Jetta, Deekshitha, Hua, Susan Z.
• Format: Article
• Language: English
• Subjects: Actinin; adherens junction (AJ); Adhesion tests; Adhesives; Cancer; Cell adhesion & migration; Cell culture; Cell interactions; Cell migration; Cell-cell contact; Channels; Coatings; Crosslinking; Cytoskeletal forces; E-cadherin; Epithelial cells; Fluorescence resonance energy transfer; Intercellular adhesion; Kinases; Microfluidic channel; Microfluidics; Proteins; Shear stress; Substrates; Wound healing
• ISSN: 0021-9290; 1873-2380
• DOI: 10.1016/j.jbiomech.2018.02.002

Collective cell movement is critical in pathological processes such as wound healing and cancer invasion. It entails complex interactions between adjacent cells and between cells-extracellular matrices. Most studies measure the migration patterns and force propagation by placing cells on flat, patterned substrates. The cooperative behavior resulting from cell-cell interactions is not well understood. We have developed a multi-channel microfluidic device that has junctional protein E-cadherin coated onto the sidewalls of the channels that enables the cells’ lateral interactions with their neighbors to be studied. Our study reveals that epithelial cells rely on lateral E-cadherin-based adhesions to maintain the cohesion of the group. Cells move faster in narrower channels, but the average velocity along the channels is reduced in E-cadherin coated channels versus non-adhesive channels. We have directly measured the forces in the cross-linking protein, alpha-actinin, using FRET sensors during cell migration, and found that higher tension exists at the cell edges adjacent to the walls coated with E-cadherin, the implication being E-cadherin transmits the shear forces but does not provide a driving force for this migration.