Biomechanics and Modeling in Mechanobiology

, Volume 15, Issue 6, pp 1557–1576 | Cite as

Gating mechanism of mechanosensitive channel of large conductance: a coupled continuum mechanical-continuum solvation approach

  • Liangliang Zhu
  • Jiazhong Wu
  • Ling Liu
  • Yilun Liu
  • Yuan Yan
  • Qiang Cui
  • Xi ChenEmail author
Original Paper


Gating transition of the mechanosensitive channel of large conductance (MscL) represents a good example of important biological processes that are difficult to describe using atomistic simulations due to the large (submicron) length scale and long (millisecond) time scale. Here we develop a novel computational framework that tightly couples continuum mechanics with continuum solvation models to study the detailed gating behavior of E. coli-MscL. The components of protein molecules are modeled by continuum elements that properly describe their shape, material properties and physicochemical features (e.g., charge distribution). The lipid membrane is modeled as a three-layer material in which the lipid head group and tail regions are treated separately, taking into account the fact that fluidic lipid bilayers do not bear shear stress. Coupling between mechanical and chemical responses of the channel is realized by an iterative integration of continuum mechanics (CM) modeling and continuum solvation (CS) computation. Compared to previous continuum mechanics studies, the present model is capable of capturing the most essential features of the gating process in a much more realistic fashion: due mainly to the apolar solvation contribution, the membrane tension for full opening of MscL is reduced substantially to the experimental measured range. Moreover, the pore size stabilizes constantly during gating because of the intricate interactions of the multiple components of the system, implying the mechanism for sub-conducting states of MscL gating. A significant fraction (\(\sim \)2/3) of the gating membrane strain is required to reach the first sub-conducting state of our model, which is featured with a relative conductance of 0.115 to the fully opened state. These trends agree well with experimental observations. We anticipate that the coupled CM/CS modeling framework is uniquely suited for the analysis of many biomolecules and their assemblies under external mechanical stimuli.


Mechanosensitive channel Gating mechanism Continuum mechanics Continuum solvation model Multi-scale simulations 



X.C. acknowledges additional support from National Natural Science Foundation of China (11172231, 11372241 and 11572238), Advanced Research Projects Agency-Energy (DE-AR0000396) and Air Force Office of Scientific Research (FA9550-12-1-0159).


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Liangliang Zhu
    • 1
    • 2
  • Jiazhong Wu
    • 1
  • Ling Liu
    • 3
  • Yilun Liu
    • 1
  • Yuan Yan
    • 1
  • Qiang Cui
    • 4
  • Xi Chen
    • 2
    Email author
  1. 1.International Center for Applied Mechanics, State Key Laboratory for Strength and Vibration of Mechanical Structures, School of AerospaceXi’an Jiaotong UniversityXi’anPeople’s Republic of China
  2. 2.Columbia Nanomechanics Research Center, Department of Earth and Environmental EngineeringColumbia UniversityNew YorkUSA
  3. 3.Department of Mechanical and Aerospace EngineeringUtah State UniversityLoganUSA
  4. 4.Department of Chemistry and Theoretical Chemistry InstituteUniversity of Wisconsin-MadisonMadisonUSA

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