(599bf) Intermediate Filaments Stiffen and Immobilize the Nucleus in Adherent Cells

The role of the cytoskeleton in homeostatic positioning of the nucleus is poorly understood. To understand the cytoskeletal components that preserve the shape and position of the cell nucleus against intracellular and extracellular forces, we observed the response of nuclei to a local, nanoNewton-scale pulling force with a micropipette applied directly to the nuclear surface in adherent living cells.  Nuclei responded to force by deforming in the direction of force but with little net translation.  Release of the force resulted in rapid restoration of the nucleus to the original shape and position.  This elastic response to the applied force depended strongly on the presence of intermediate filaments. Nuclei in cells devoid of vimentin exhibited much greater deformation and translation, whereas deformation of nuclei in lamin A/C null cells was inelastic and irreversible. Actin microfilaments and microtubules contributed little to the nuclear response. These findings demonstrate that intermediate filaments play a critical role in preserving the shape and position of the cell nucleus in living adherent cells.