How cytoskeletal forces alter nuclear protein and chromatin distributions during confined cell migration.

The ability of cells to squeeze through constrictions is affected by the stiffness of the large and rigid nucleus, and is a hallmark of metastases and cancer progression. During this process, a sufficient force needs to be applied by the cytoskeleton to the nucleus. We address here the mechanism of nucleus pulling during cell translocation through openings smaller than the nuclear diameter. We observe its consequences on the chromatin distribution. We showed that nuclear envelope proteins, such as nesprins, which mechanically link the actin cytoskeleton to the nuclear membrane, move towards the front of the nucleus surface, a movement that depends on pulling forces, especially through the actin cytoskeleton [1]. Likewise, SUN proteins move towards the nucleus front  whereas the lamin network, right underneath the nucleus membrane, does not polarize. The lamin shell wrinkles during nucleus translocation and chromatin densifies at the center of the nucleus. Our results allow for deciphering the orchestration of mechanotransduction in the nucleus and suggest an active/passive role repartition among those proteins. The next step will be to characterize and quantify this repartition, in particular when motility is increased.