Fig. 3.

Nuclei with low levels of lamin A,C and round morphologies are indented by the MTOC. Microtubules in large and elongated cells buckle without being able to significantly indent the nucleus as the MTOC is pushed toward the cell boundary by the nucleus (A and C). In contrast, cells on small and circular substrates exhibit crescent-shaped nuclear morphologies as the MTOC pushes against the nucleus and forms a local indentation in the nucleus (B and D). Similar to the circular cell, the nucleus is indented by the MTOC when actin filaments are depolymerized in the rectangular cell (E). Overexpression of lamin A,C (F) and nocodazole treatment (G) rescue nuclear invagination in circular cells. Cell geometric constraints and polymerization of microtubules reduce nuclear lamina stiffness by decreasing actomyosin contractility (H); compared with small and circular cells (i), cells on large and elongated substrates (ii) show increased contractility which in turn leads to stiffening of the nuclear envelope lamina network in proportion to actomyosin-driven tension in the nuclear envelope. Depolymerization of microtubules in large and elongated cells (iii) further increases actomyosin contractility and subsequently nuclear lamina stiffness. The actomyosin-driven reduction in nuclear height tenses and stiffens the nuclear envelope lamina network (I).