Mechanical effects in NPCs. NPCs are composed of cytoplasmic and nuclear filaments (forming the nuclear basket in the nuclear case, gray), the cytoplasmic and nuclear rings (light green), the inner ring that lines the central channel (dark green), and the FG-nup proteins that form the permeability barrier (gray). Force transmission to the nucleus can occur non-specifically (for instance, as cells migrate through small constrictions) or specifically through the LINC complex (formed by SUN and nesprin proteins, right), which links actin filaments to the nuclear lamina. Regarding the graphs in the central channel, from left to right: passive transport is increased by force applied to the nucleus, but only for small MW proteins. In contrast, active/facilitated transport (in which cargo proteins are bound to nuclear transport receptors such as importins) is affected regardless of MW. Diffusion through nuclear pores is also affected by protein mechanical stability, and the chemical composition of surface-exposed residues (marked with the different residues associated with low/high diffusion). In principle, the effect of these two factors should apply both for passive and facilitated transport. Although not tested, these two factors could also regulate mechanosensitivity in a manner similar to MW.