(158m) Membrane Fusion Allows Ruptureless Extreme Deformation of Nuclei during Cell Migration

During migration of cells through narrow spaces, the nucleus undergoes extreme deformation. Such deformation is frequently accompanied by rupture of the nuclear envelope. Nuclear rupture has been implicated in pathogenesis mechanisms, however, the mechanisms by which the nucleus ruptures are not fully understood. Here we tracked fibroblasts as they migrated through vertical PDMS obstacles. Nuclei underwent extreme deformations around the posts. Interestingly, nuclei did not rupture when opposing nuclear surfaces fused with each other. Conversely, nuclei ruptured when such fusion was not possible. Quantification of nuclear perimeter revealed that dynamic membrane fusion relieved strain in the nuclear surface during deformation which likely allowed escape from rupture. These results suggest that remodeling of the nuclear envelope can allow extreme nuclear deformations without envelope rupture.