title: Gating mechanisms of mechanosensitive channels of large conductance, I: a continuum mechanics-based hierarchical framework.
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 used to explore the detailed gating mechanisms of the MscL in Escherichia coli embedded in a palmitoyloleoylphosphatidylethanolamine lipid bilayer. In Part I of this study, 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 study, the detailed gating mechanisms of E. coli-MscL under various types of loading are presented and compared with experiments, structural model, and 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.
authors.affiliation: Nanomechanics Research Center, Department of Civil Engineering and Engineering Mechanics, Columbia University, New York, New York 10027, USA. xichen@civil.columbia.edu
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Qiang
authors.initials: Q
authors.lastname: Cui
authors.forename: Yuye
authors.initials: Y
authors.lastname: Tang
authors.forename: Jejoong
authors.initials: J
authors.lastname: Yoo
authors.forename: Arun
authors.initials: A
authors.lastname: Yethiraj
mesh_terms: D003198:Computer Simulation; D004548:Elasticity; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000502:physiology* / Q000648:ultrastructure; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry* / Q000502:physiology* / Q000648:ultrastructure; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008954:Models, Biological; D008956:Models, Chemical; D008958:Models, Molecular; D011789:Quantum Theory; D013314:Stress, Mechanical
chemical_list: D029968:Escherichia coli Proteins; D007473:Ion Channels; C086596:MscL protein, E coli