Shear Stress Induced Calcium Dependent Nuclear Deformation in Epithelial Cells

Abstract

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 Ca2+ under fluid shear stress in MDCK cells using a parallel plate microfluidic chip. We show that fluid shear stress (1.1 dyn/cm2, 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 Ca2+ is required for shear induced nucleus deformation. Inhibiting Ca2+ influx with GsMTx4 and Gd3+ eliminated Ca2+ influx and abolished the nuclear deformation. The cytoskeleton reorganization occurred in parallel with Ca2+ rise in the cells. Increasing intracellular Ca2+ with thapsigargin that depletes the Ca2+ stores resumed the nuclear deformation. This suggests that shear induced nuclear deformation is a Ca2+ dependent process.