Modeling of mechanosensitive channel gating in response to wall shear stress |
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Authors: | Shigeru Tada Satoshi Akiyama |
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Affiliation: | 1. Department of Applied Physics, National Defense Academy, 1-10-20 Hashirimizu, Yokosuka, Kanagawa, 239-8686, Japan
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Abstract: | The accurate biological function of mechanosensitive (MS) channels is crucial for maintaining the viability of living cells. For instance, in vascular endothelial cells, calcium influx from the extracellular environment into cytoplasm is regulated by stretch-activated channels. However, the mechanism by which cells sense force remains unclear. For this study, we hypothesized that gating of ion channels is simply regulated by the direct mechanical stress induced in a membrane. We modeled a membrane channel using crystallographic data of the bacteria Mycobacterium tuberculosis (Tb-MscL) because MscL homologs are integral membrane proteins with sequence similarity to most known ion channels. Molecular dynamics (MD) simulations were performed to elucidate the gating mechanism of the channel protein in response to the fluid shear stress. Results suggest that the stretched membrane drives the interfacial part of the protein–membrane complex to expand and maintains the stability of the constricted part of the transmembrane pore. Moreover, structural similarities between Tb-MscL and the family of ligand-gated ion channels suggest that the conformational change of this model in response to fluid shear stress is useful for modeling the gating mechanism in a broad class of gated channels. |
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