BIOPHYSICAL THEORY AND MODELING |
Gating Mechanisms of Mechanosensitive Channels of Large Conductance Part I: A Continuum Mechanics-Based Hierarchical Framework
Xi Chen 1*, Qiang Cui 2, Yuye Tang 1, Jejoong Yoo 3 and Arun Yethiraj 4
1 Columbia University
2 University of Wisconsin, Madison
3 University of Wisconsin-Madison
4 University of Wisconsin
* To whom correspondence should be addressed. E-mail: xichen{at}civil.columbia.edu.
Submitted on December 27, 2007
Revised on January 23, 2008
Accepted on 18 March 2008
 |
Abstract |
|---|
A hierarchical simulation framework that integrates information from molecular dynamics (MD) simulations into a continuum model is established to study the mechanical response of mechanosensitive channel of large conductance (MscL) using the finite element method (FEM). The proposed MD-decorated FEM (MDeFEM) approach is employed to explore the detailed gating mechanisms of the MscL in bacteria Escherichia Coli (E.coli) embedded in a palmitoyloleoylphosphatidylethanolamine (POPE) lipid bilayer. In Part I of this paper, the framework of MDeFEM is established. The transmembrane and cytoplasmic helices are taken to be elastic rods, the loops are modeled as springs, and the lipid bilayer is approximated by a three-layer sheet. The mechanical properties of the continuum components, as well as their interactions, are derived from molecular simulations based on atomic force fields. In addition, analytical closed-form continuum model and elastic network model are established to complement the MDeFEM approach and to capture the most essential features of gating. In Part II of this paper, the detailed gating mechanisms of E.Coli-MscL under various types of loading are presented and compared with experiments, structural model, all-atom simulations, as well as the analytical models established in Part I. It is envisioned that such a hierarchical multiscale framework will find great value in the study of a variety of biological processes involving complex mechanical deformations such as muscle contraction and mechanotransduction.
Key Words:
elastic network model, finite element analysis, gating, mechanosensitive channel
