Fig. 14. Suggested model for mechanosensitive nucleocytoplasmic shuttling of YAP. (A) On soft substrates, the nucleus is mechanically uncoupled from the substrate and not submitted to forces. The import and export of YAP through nuclear pores are balanced. (B) On stiff substrates, focal adhesions and stress fibers (F-actin) are formed, the forces are applied to the nucleus and leads to flattening. This process led to stretching and curving nuclear pores that increased YAP import from the cytoplasm to nuclear. (C) Transmission through these pores depends on two factors: molecular weight and mechanical stability. Proteins with lower molecular weight or lower mechanical stability (easily unfolded protein) can pass through these pores much more easily. This is a general rule for transmission through such pores, which also includes the Yep molecule (Reprinted with permission, Cell Press, for citation see [119]).