期刊
JOURNAL OF THE MECHANICS AND PHYSICS OF SOLIDS
卷 133, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmps.2019.103705
关键词
Nuclear pore complex; Mechanotransduction; Bi-stable Switches; Debye screening
资金
- National Natural Science Foundation of China [11522219, 11532009, 11902155, 11972280]
- New Faculty Foundation of NUAA [1001-YAH19016]
- foundation of Jiangsu Provincial Key Laboratory of Bionic Functional Materials [1001-XCA1816310]
- Foundation for the Priority Academic Program Development of Jiangsu Higher Education Institutions
- National Science Foundation through the Science and Technology Center for Engineering Mechanobiology [CMMI 1548571]
- National Institutes of Health [U01EB016422]
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.
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