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bioRxiv · 10.1101/2023.09.05.556369

Vinculin is Essential For Sustaining Normal Levels of Endogenous Force Transmission at Cell-Cell Contacts

Mezher, M.·Dumbali, S.·Fenn, I.·Lamb, C.·Miller, C.·Cabe, J. I.·Bejar-Padilla, V.·Conway, D.·Maruthamuthu, V.
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Abstract

Transmission of cell-generated (i.e., endogenous) tension at cell-cell contacts is crucial for tissue shape changes during morphogenesis and adult tissue repair in tissues like epithelia. E-cadherin-based adhesions at cell-cell contacts are the primary means by which endogenous tension is transmitted between cells. The E-cadherin-{beta}-catenin--catenin complex mechanically couples to the actin cytoskeleton (and thereby the contractile machinery of the cell) both directly and indirectly. However, the key adhesion constituents required for substantial endogenous force transmission at these adhesions in cell-cell contacts are unclear. Due to the role of -catenin as a mechanotransducer that recruits vinculin at cell-cell contacts, we expected -catenin to be essential for the high levels of force transmission normally sustained. Instead, using the traction force imbalance method to determine the inter-cellular force at a single cell-cell contact between cell pairs, we found that it is vinculin that is essential for high endogenous force transmission. Our results constrain the potential mechanical pathways of force transmission at cell-cell contacts and suggest that vinculin can transmit forces at E-cadherin adhesions independent of -catenin, possibly through {beta}-catenin. Furthermore, we tested the ability of cell-cell contacts to withstand external stretch and found that vinculin is essential to maintain cell-cell contact stability under external forces as well.

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Mezher, M., Dumbali, S., Fenn, I., Lamb, C., Miller, C., Cabe, J. I., Bejar-Padilla, V., Conway, D., Maruthamuthu, V.. 2023-09-06. Vinculin is Essential For Sustaining Normal Levels of Endogenous Force Transmission at Cell-Cell Contacts. https://doi.org/10.1101/2023.09.05.556369

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