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. 2018 May 7;217(5):1571–1587. doi: 10.1083/jcb.201701039

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© 2018 Broders-Bondon et al.

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Figure 3. — Nucleomechanotransduction. (a) The LINC connects the cytoskeleton to the nucleus through SUN proteins anchored in the inner nuclear membrane and Nesprins anchored in the outer nuclear membrane. Mechanical stress transmission (red stars) occurs through integrins, F-actin, Nesprin, and SUN proteins. Under tension, Lamin-A and -C proteins are assembled in the nuclear lamina then dephosphorylated, leading to protein unfolding, a decrease of solubility, and strengthening of the lamina. Cyt, cytoplasm; i.n.m, inner nuclear membrane; o.n.m, outer nuclear membrane; p.m., plasma membrane. (b) Cell and nuclear deformation occurs during migration through narrow constrictions of the ECM. Yellow depicts the actin–myosin network applying contractile forces onto the nucleus. (c) Cell migration through micrometer-sized constrictions provokes mislocalization of DNA-repair factors, causing DNA damage and leading to permanent heterogeneity in chromosome copy numbers, expression levels, cell shape, and migration ability (Irianto et al., 2017).