A finite element framework for studying the mechanical response of macromolecules: Application to the gating of the mechanosensitive channel MscL

Yuye TANG, Guoxin CAO, Xi CHEN*, Jejoong YOO, Arun YETHIRAJ, Qiang CUI

*Corresponding author for this work

Research output: Journal PublicationsJournal Article (refereed)peer-review

69 Citations (Scopus)

Abstract

The gating pathways of mechanosensitive channels of large conductance (MscL) in two bacteria (Mycobacterium tuberculosis and Escherichia coli) are studied using the finite element method. The phenomenological model treats transmembrane helices as elastic rods and the lipid membrane as an elastic sheet of finite thickness; the model is inspired by the crystal structure of MscL. The interactions between various continuum components are derived from molecular-mechanics energy calculations using the CHARMM all-atom force field. Both bacterial MscLs open fully upon in-plane tension in the membrane and the variation of pore diameter with membrane tension is found to be essentially linear. The estimated gating tension is close to the experimental value. The structural variations along the gating pathway are consistent with previous analyses based on structural models with experimental constraints and biased atomistic molecular-dynamics simulations. Upon membrane bending, neither MscL opens substantially, although there is notable and nonmonotonic variation in the pore radius. This emphasizes that the gating behavior of MscL depends critically on the form of the mechanical perturbation and reinforces the idea that the crucial gating parameter is lateral tension in the membrane rather than the curvature of the membrane. Compared to popular all-atom-based techniques such as targeted or steered molecular-dynamics simulations, the finite element method-based continuum-mechanics framework offers a unique alternative to bridge detailed intermolecular interactions and biological processes occurring at large spatial scales and long timescales. 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. © 2006 by the Biophysical Society.
Original languageEnglish
Pages (from-to)1248-1263
Number of pages15
JournalBiophysical Journal
Volume91
Issue number4
DOIs
Publication statusPublished - 15 Aug 2006
Externally publishedYes

Bibliographical note

The work of Y.T., G.C., and X.C. is supported in part by the National Science Foundation grant No. CMS-0407743 and in part by the Academic Quality Fund of Columbia University. J.Y. is partially supported by a grant from the National Institutes of Health (No. R01-GM071428 to Q.C.). Q.C. is an Alfred P. Sloan Research Fellow.

Fingerprint

Dive into the research topics of 'A finite element framework for studying the mechanical response of macromolecules: Application to the gating of the mechanosensitive channel MscL'. Together they form a unique fingerprint.

Cite this