The study of the gating mechanism of mechanosensitive channels opens a window to the exploration of how different mechanical stimuli induce adaptive cellular behaviors of both the protein and the lipid, across different time and length scales. In this work, through a molecular dynamics-decorated finite element method (MDeFEM), the gating behavior of mechanosensitive channels of small conductance (MscS) in Escherichia coli (E. coli) is studied upon membrane stretch or global bending. The local membrane curvature around MscS is incorporated, as well as multiple MscL (mechanosensitive channels of large conductance) molecules in proximity to MscS. The local membrane curvature is found to delay MscS opening and diminishes moderately upon membrane stretching. Mimicking the insertion of lysophosphatidylcholine (LPC) molecules into the lipid, both downward and upward bending can active MscS, as long as the global membrane curvature radius reaches 34 nm. Based on the different MscS pore evolutions observed with the presence of one or more MscLs nearby, we propose that when coreconstituted, multiple MscL molecules tend to be located at the local membrane curvature zone around MscS. In another word, as MscL “swims around” in the lipid bilayer, it can be trapped by the membrane's local curvature. Collectively, the current study provides valuable insights into the interplay between mechanosensitive channels and lipid membrane at structural and physical levels, and specific predictions are proposed for further experimental investigations. © 2019 Elsevier Ltd
|Journal||Journal of the Mechanical Behavior of Biomedical Materials|
|Publication status||Published - 2020|
Bibliographical noteThis work was supported by the National Natural Science Foundation of China (11572238 and 11872302), Key R & D Program of Shaanxi (2018ZDXM-GY-131), and Earth Engineering Center and Center for Advanced Materials for Energy and Environment at Columbia University.
- Cooperative gating
- Local membrane curvature
- MscL localization