  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 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 et al. (2002), Powl et al. (2003),
Yoshimura et al. (2004), and others and suggest a suite of new experiments.
