Role of fluid shear stress on E-cadherin dynamics and cytoskeletal stresses

Adherens junctions (AJs) play an important role in cell-cell mechanical coupling and in maintaining tissue organization. Under chronic flow, epithelial cells adapt by strengthening cell-cell junctions in order to maintain the integrity of epithelia. How forces due to fluid flow are transmitted to E-cadherin and cause the dynamic remodeling of AJs is unclear. In this study we simultaneously measured AJ dynamics and cytoskeletal stresses and reorganization in MDCK cells under flow. The cells were co-expressed with fluorescently labelled E-cadherin and stress sensitive α-actinin FRET sensor for measurements. A fluid shear stress of 0.7dyn/cm2for 3 hours caused an increase in expression of E-cadherin, formation of new AJs and strengthening of pre-existing AJs leading to a continuous distribution of cell-cell junctions. This increase in cell-cell junctions is correlated with the formation of strong peripheral actin ring due to cytoskeleton reorganization. The average cytoskeletal stress at adherens junctions shows multi-phase changes under flow, which closely links to the dynamic changes of AJs. These results provide the direct evidence that the shear stress induced cytoskeletal forces play an important role on cell-cell adhesions.