Membrane-protein interactions in mechanosensitive channels

¹ Caltech

^* To whom correspondence should be addressed. E-mail: pwiggins{at}caltech.edu.

Submitted on June 24, 2004
Revised on August 23, 2004
Accepted on 29 October 2004

	Abstract

In this paper, we examine the mechanical role of the lipid bilayer in ion channel conformation and function with specific reference to the case of the mechanosensitive channel of large conductance (MscL). In a recent paper (Wiggins and Phillips, 2004), we argued that mechanotransduction very naturally arises from lipid-protein interactions by invoking a simple analytic model of the MscL channel and the surrounding lipid bilayer. In this paper, we focus on improving and expanding this analytic framework for studying lipid-protein interactions with special attention to MscL. Our goal is to generate simple scaling relations which can be used to provide qualitative understanding of the role of membrane mechanics in protein function and to quantitatively interpret experimental results. For the MscL channel, we find that the free energies induced by lipid-protein interaction are of the same order as the free energy differences between conductance states measured by Sukharev {\it et al.} (1999). We therefore conclude that the mechanics of the bilayer plays an essential role in determining the conformation and function of the channel. Finally, we compare the predictions of our model to experimental results from the recent investigations of the MscL channel by Perozo {\it et al.} (2002a,b), Powl {\it et al.} (2003), Yoshimura {\it et al.} (2004), and others and suggest a suite of new experiments.

Key Words: Mechanotransduction, channel gating, lipid-protein interaction

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