Electrostatic switching of nuclear basket conformations provides a potential mechanism for nuclear mechanotransduction

Cells can respond to mechanical forces by changing gene expression. Changes to transport through pores in the nuclear membrane have been implicated in these responses, but the mechanisms by which stress-dependent, selective nuclear transport occur have not been elucidated. We identified a potential mechanism for this via stretch-dependent switching behavior in nuclear pore complexes (NPCs). NPCs, composed of proximal and distal rings connected by a basket of filaments within the nucleus, form channels for the selective transport through the nuclear membrane. Our simulations showed that the relatively narrow NPC distal ring, long believed to responsible for channel gating and selectivity, cannot stretch to accommodate larger molecules. Instead, our results suggested that rapid phase transitions in nuclear basket filament conformations could serve to regulate large molecule transport. Nuclear basket conformations were bi-stable under certain conditions within the physiological range, enabling strong sensitivity to the mechanical state of the nuclear membrane, and suggesting a possible pathway for mechanosensitive nuclear gating. (C) 2019 Elsevier Ltd. All rights reserved.