Cytoskeletal control of nuclear morphology and stiffness are required for OPN-induced bone marrow-derived mesenchymal stem cell migration.

During cell migration, the movement of the nucleus must be coordinated with the cytoskeletal dynamics that influence the efficiency of cell migration. Our previous study demonstrated that osteopontin (OPN) significantly promotes the migration of bone marrow-derived mesenchymal stem cells (BMSCs). However, the mechanism of regulation of nuclear mechanics by the cytoskeleton during OPN-promoted BMSC migration remains unclear. In the present study, we investigated how the actin cytoskeleton influences nuclear mechanics in BMSCs. We assessed the morphology and mechanics of the nuclei in the OPN-treated BMSCs subjected to disruption or polymerization of the actin cytoskeleton. We found that disruption of actin organization by cytochalasin D (Cyto D) resulted in a decrease in the nuclear projected area and nuclear stiffness. Stabilization of actin assembly by jasplakinolide (JASP) resulted in an increase in the nuclear projected area and nuclear stiffness. SUN1 (Sad-1/UNC-84 1) is a component of the LINC (linker of nucleoskeleton and cytoskeleton) complex involved in the connections between the nucleus and the cytoskeleton. We found that SUN1 depletion by RNAi decreased the nuclear stiffness and OPN-promoted BMSC migration. Thus, F-actin cytoskeleton plays an important role in determining the morphology and mechanical properties of the nucleus. We suggest that the cytoskeletal-nuclear interconnectivity through the SUN1 proteins plays an important role in the OPN-promoted BMSC migration.