The Combined Effect of Hydrophobic Mismatch and Bilayer Local Bending on the Regulation of Mechanosensitive Ion Channels.

Omid Bavi,Yousef Jamali,Reza Naghdabadi,Manouchehr Vossoughi,Hendrik W Van Veen

doi:10.1371/journal.pone.0150578

Abstract

The hydrophobic mismatch between the lipid bilayer and integral membrane proteins has well-defined effect on mechanosensitive (MS) ion channels. Also, membrane local bending is suggested to modulate MS channel activity. Although a number of studies have already shown the significance of each individual factor, the combined effect of these physical factors on MS channel activity have not been investigated. Here using finite element simulation, we study the combined effect of hydrophobic mismatch and local bending on the archetypal mechanosensitive channel MscL. First we show how the local curvature direction impacts on MS channel modulation. In the case of MscL, we show inward (cytoplasmic) bending can more effectively gate the channel compared to outward bending. Then we indicate that in response to a specific local curvature, MscL inserted in a bilayer with the same hydrophobic length is more expanded in the constriction pore region compared to when there is a protein-lipid hydrophobic mismatch. Interestingly in the presence of a negative mismatch (thicker lipids), MscL constriction pore is more expanded than in the presence of positive mismatch (thinner lipids) in response to an identical membrane curvature. These results were confirmed by a parametric energetic calculation provided for MscL gating. These findings have several biophysical consequences for understanding the function of MS channels in response to two major physical stimuli in mechanobiology, namely hydrophobic mismatch and local membrane curvature.

Highlights

Studies of integral membrane proteins have demonstrated that their function is dynamically modulated by the surrounding lipid bilayer [1, 2]
Previous studies of MS channels have already shown the importance of membrane tension in the gating of bacterial channels [7, 8] and small antibiotic peptides such as Gramicidin A [9], and for eukaryotic channels such as TRPV4, TREK, TRAAK and PIEZO1 [10,11,12,13]
Our Finite Element (FE) simulations examined the effect of positive and negative local membrane bending on the MscL pore shape in three different cases; (i) positive protein-lipid hydrophobic mismatch (Fig 2); (ii) zero mismatch (Fig 3); and (iii) negative hydrophobic mismatch (Fig 4)

Summary

Introduction

Studies of integral membrane proteins have demonstrated that their function is dynamically modulated by the surrounding lipid bilayer [1, 2]. Many of these membrane proteins, in PLOS ONE | DOI:10.1371/journal.pone.0150578. Bilayer Local Bending, Hydrophobic Mismatch and Gating of MscL particular mechanosensitive (MS) ion channels, interact with annular lipids of the bilayer via tight hydrophobic and/or electrostatic interactions [2,3,4]. Two important physical factors that have a major role in the gating of MS channels are protein-lipid hydrophobic mismatch and membrane curvature

Methods

Results

Conclusion