Numerical Simulation of Nanoindentation and Patch Clamp Experiments on Mechanosensitive Channels of Large Conductance in <Emphasis Type="Italic">Escherichia coli</Emphasis> |
| |
| Authors: | Y Tang X Chen J Yoo A Yethiraj Q Cui |
| |
| Institution: | (1) Nanomechanics Research Center, Department of Civil Engineering and Engineering Mechanics, Columbia University, New York, NY 10027, USA;(2) Theoretical Chemistry Institute, Department of Chemistry, University of Wisconsin at Madison, Madison, WI 53706, USA |
| |
| Abstract: | A hierarchical simulation framework that integrates information from all-atom simulations into a finite element model at the
continuum level is established to study the mechanical response of a mechanosensitive channel of large conductance (MscL)
in bacteria Escherichia coli (E. coli) embedded in a vesicle formed by the dipalmitoylphosphatidycholine (DPPC) lipid bilayer. Sufficient structural details of
the protein are built into the continuum model, with key parameters and material properties derived from molecular mechanics
simulations. The multi-scale framework is used to analyze the gating of MscL when the lipid vesicle is subjective to nanoindentation
and patch clamp experiments, and the detailed structural transitions of the protein are obtained explicitly as a function
of external load; it is currently impossible to derive such information based solely on all-atom simulations. The gating pathways
of E. coli-MscL qualitatively agree with results from previous patch clamp experiments. The gating mechanisms under complex indentation-induced
deformation are also predicted. This versatile hierarchical multi-scale framework may be further extended to study the mechanical
behaviors of cells and biomolecules, as well as to guide and stimulate biomechanics experiments. |
| |
| Keywords: | Mechanosensitive channel Nanoindentation Patch clamp Finite element simulation |
| 本文献已被 SpringerLink 等数据库收录！ |
|
