Spatial distribution of cell-cell and cell-ECM adhesions regulates force balance while main-taining E-cadherin molecular tension in cell pairs

• Published in: Molecular biology of the cell 2015-07, Vol.26 (13), p.2456-2465
• Main Authors: Sim, Joo Yong, Moeller, Jens, Hart, Kevin C, Ramallo, Diego, Vogel, Viola, Dunn, Alex R, Nelson, W James, Pruitt, Beth L
• Format: Article
• Language: English
• Subjects: Animals; Biomechanical Phenomena; Cadherins - metabolism; Cell Adhesion - physiology; Cell Shape - physiology; Cell-Matrix Junctions - physiology; Dogs; Extracellular Matrix - metabolism; Madin Darby Canine Kidney Cells; Models, Biological
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.e14-12-1618

Mechanical linkage between cell-cell and cell-extracellular matrix (ECM) adhesions regulates cell shape changes during embryonic development and tissue homoeostasis. We examined how the force balance between cell-cell and cell-ECM adhesions changes with cell spread area and aspect ratio in pairs of MDCK cells. We used ECM micropatterning to drive different cytoskeleton strain energy states and cell-generated traction forces and used a Förster resonance energy transfer tension biosensor to ask whether changes in forces across cell-cell junctions correlated with E-cadherin molecular tension. We found that continuous peripheral ECM adhesions resulted in increased cell-cell and cell-ECM forces with increasing spread area. In contrast, confining ECM adhesions to the distal ends of cell-cell pairs resulted in shorter junction lengths and constant cell-cell forces. Of interest, each cell within a cell pair generated higher strain energies than isolated single cells of the same spread area. Surprisingly, E-cadherin molecular tension remained constant regardless of changes in cell-cell forces and was evenly distributed along cell-cell junctions independent of cell spread area and total traction forces. Taken together, our results showed that cell pairs maintained constant E-cadherin molecular tension and regulated total forces relative to cell spread area and shape but independently of total focal adhesion area.