Deciphering how forces pull the nucleus during confined cell motility.

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. What is the mechanism of nucleus pulling during cell translocation through openings smaller than the nuclear diameter is what we address here.We recently showed that nuclear envelope proteins, such as nesprins, which mechanically link the actin cytoskeleton to the nuclear membrane, move towards the front at the surface of the nucleus¹. SUN proteins follow the movement of nesprins. Moreover, we demonstrated that nesprin movement is initiated by the actin cytoskeleton which redistributes nesprins on the nuclear membrane and contributes to pulling. Myosin have a complementary role. We thus reveal one gear of the “mechanostransduction” chain between the cytoskeleton and the nucleoskeleton.

Reference:

1. Davidson PM, Battistella A, Déjardin T, Betz T, Plastino J, Borghi N, et al. Nesprin 2 accumulates at the front of the nucleus during confined cell migration. EMBO reports 2020, 21(7).