Figure 2.

Proposed mechanisms for how the cell nucleus could respond directly to mechanical forces. (1) Stretching of the nuclear membrane could alter the conformation of the rough ER, exposing more ribosomes to the cytoplasm. (2) Force application promotes translocation of emerin from the INM to the ONM, modulating chromatin organization and facilitating actin polymerization at the ONM. (3) Increased membrane tension could open nuclear pore complexes (NPC) and modulate NPC permeability. (4) Stretching of the nuclear membrane recruits cPLA2 to the INM. (5) Force transmission to the nucleus results in post-translational modification and altered dynamics of lamin A/C and INM proteins such as emerin (see also (2)), which can modulate the mechanical properties of the nucleus and induce downstream signaling. (6) External forces can induce chromatin stretching, altering polymerase and transcription factor accessibility and activity. (7) Nuclear pore opening and sequestration at the nuclear envelope can modulate localization and activity of transcription factors. (8) Forces acting on the nucleus may reposition chromatin domains, altering their transcriptional activity. (9) Mechanically induced polymerization of nuclear actin can modulate export and activity of the transcriptional regulator MKL1, and affect other nuclear processes that require monomeric actin.