The role of activity from within and outside of the cell nucleus in nuclear blebbing

The cell nucleus is an active environment in which molecular motors such as RNA polymerase and condensin continuously remodel chromatin. Outside the nucleus, the cytoskeleton is an active semiflexible polymer network comprised of actin, microtubules, and intermediate filaments, with motors, such as myosin and kinesin, remodeling the network. These two active environments are mechanically coupled via LINC complexes embedded in the nuclear membranes, as well as direct steric interactions at their interface. We numerically study shape fluctuations at the interface of these two active environments. We focus on the formation of nuclear blebs, which are large bulges in the nuclear envelope that frequently occur in the cells of individuals with diseases, such as muscular dystrophy or progeria. In particular, we study how bleb formation depends on the type of activity in the nucleus, be it contractile or extensile, to explain such phenomena as nuclear blebs occurring more frequently for diseased cells in stiffer or more confined microenvironments than in softer ones.