Shear stress induced calcium dependent nuclear deformation in epithelial cells

External mechanical forces can reach the cell nucleus causing changes in nuclear morphology, size and motility. A common explanation is that these forces are transmitted by surrounding cytoskeleton network through its linkage to nuclear envelope; shear stress causes reorganization of cytoskeleton, thus, the changes in nuclear shape. In this study, we measured nuclear shape and intracellular Ca ²⁺ under fluid shear stress in MDCK cells using a parallel plate microfluidic chip. We show that fluid shear stress (1.1 dyn/cm ² , 3 hrs) causes significant changes in nuclear shape in cells, from a flat disk shape having larger area to a thicker disk having smaller area. An increase in intracellular Ca ²⁺ is required for shear induced nucleus deformation. Inhibiting Ca ²⁺ influx with GsMTx4 and Gd3+ eliminated Ca ²⁺ influx and abolished the nuclear deformation. The cytoskeleton reorganization occurred in parallel with Ca ²⁺ rise in the cells. Increasing intracellular Ca ²⁺ with thapsigargin that depletes the Ca ²⁺ stores resumed the nuclear deformation. This suggests that shear induced nuclear deformation is a Ca ²⁺ dependent process.