Gating Mechanism of Mechanosensitive Ion Channels Studied by Continuum Mechanics

Abstract

To complement the existing experimental and computational methods used for studies of membrane protein structure and dynamics a finite element (FE) model for multi length-scale and time-scale investigations of the gating mechanism of mechanosensitive (MS) ion channels has been established. The main advantage of the FE simulation over molecular dynamic simulation is its flexibility in handling complex geometries and boundary conditions. In this study the FE model of MscL, the large conductance bacterial MS channel, has been developed as an initial template providing a continuum structural framework for a mechanistic understanding of the gating mechanism in MS channels, which can also be employed to develop structural dynamic models of other types of MS channels. A typical tensional force needed to activate MS channels was first applied to the FE model of the lipid bilayer and was then varied depending on the mechanical properties and cholesterol content of the membrane bilayer surrounding MscL. In agreement with the experimental results the FE model showed that adding cholesterol to the lipid bilayer caused a significant increase in the tensional force required for MscL activation. Furthermore, the current model helped to define the membrane stress distribution around a ‘hole’ in the membrane bilayer containing the MscL protein as well as to identify stress areas where the MscL protein is attached to the hole boundary by applying an appropriate mesh refinement and defining contact conditions between the channel and the bilayer. Cholesterol, although stiffening the lipid bilayer, increased the stress intensity in the highly stressed areas of the MscL protein under tension and thus facilitated rupturing of the lipid bilayer. Although initially surprising, this result is consistent with the patch clamp experiments, which demonstrated that adding cholesterol markedly reduced the bilayer lytic tension.