Mechanical force application to the nucleus regulates nucleocytoplasmic transport

Area of Science:

• Cell Biology
• Biophysics

Background:

• Mechanical forces influence cellular functions, with the nucleus sensing and responding to these forces.
• The role of mechanical force in controlling nucleocytoplasmic transport remains largely unknown.

Purpose of the Study:

• To investigate how mechanical force regulates nucleocytoplasmic transport.
• To determine the mechanism by which force affects the movement of molecules across the nuclear envelope.

Main Methods:

• Differential control of passive and facilitated nucleocytoplasmic transport was analyzed.
• The effect of nuclear force on nuclear pore complex permeability was measured.
• The molecular weight and affinity dependence of cargo translocation was assessed.

Main Results:

• Nuclear forces were shown to increase nuclear pore complex permeability.
• The molecular weight dependence of permeability was stronger for passive than facilitated diffusion.
• Force-induced translocation of cargoes was observed within specific molecular weight and affinity ranges.

Conclusions:

• Mechanical force differentially controls passive and facilitated nucleocytoplasmic transport.
• This mechanism explains the mechanosensitivity of shuttling proteins and transcriptional regulators.
• The findings reveal a novel mechanically induced signaling pathway with broad applicability.