Bilayer Thickness and Membrane Protein Function: An Energetic Perspective

Abstract

The lipid bilayer component of biological membranes is important for the distribution, organization, and function of bilayer-spanning proteins. This regulation is due to both specific lipid-protein interactions and general bilayer-protein interactions, which modulate the energetics and kinetics of protein conformational transitions, as well as the protein distribution between different membrane compartments. The bilayer regulation of membrane protein function arises from the hydrophobic coupling between the protein's hydrophobic domains and the bilayer hydrophobic core, which causes protein conformational changes that involve the protein/bilayer boundary to perturb the adjacent bilayer. Such bilayer perturbations, or deformations, incur an energetic cost, which for a given conformational change varies as a function of the bilayer material properties (bilayer thickness, intrinsic lipid curvature, and the elastic compression and bending moduli). Protein function therefore is regulated by changes in bilayer material properties, which determine the free-energy changes caused by the protein-induced bilayer deformation. The lipid bilayer thus becomes an allosteric regulator of membrane function.

Lipid Lateral Mobility in Cochlear Outer Hair Cells: Regional Differences and Regulation by Cholesterol

“…Previous studies have shown that cholesterol regulates the function of other sensory and transport proteins, including rhodopsin (Boesze-Battaglia et al 1989;Boesze-Battaglia and Albert 1990;Albert et al 1996;Albert and Boesze-Battaglia 2005), the nicotinic acetylcholine receptor (Barrantes 2007), transient receptor proteins associated with cation channel complexes (Graziani et al 2006), L-type calcium currents (Tsujikawa et al 2008), as well as a variety of ion transporters and exchangers common to many cell types (Yeagle 1991;Bastiaanse et al 1997;Andersen and Koeppe 2007). The suggested biophysical mechanism(s) responsible for these effects are diverse and include both specific lipid-protein interactions and more general membrane-protein interactions that either direct the lateral organization of proteins or modulate protein conformational changes (Yeagle 1991;Andersen and Koeppe 2007).…”

“…The suggested biophysical mechanism(s) responsible for these effects are diverse and include both specific lipid-protein interactions and more general membrane-protein interactions that either direct the lateral organization of proteins or modulate protein conformational changes (Yeagle 1991;Andersen and Koeppe 2007). Each specific protein transition has an associated energy cost which depends on the bilayer material properties, and changes in membrane fluidity may alter the kinetics of transitions between conformational states (Andersen and Koeppe 2007).…”

“…Each specific protein transition has an associated energy cost which depends on the bilayer material properties, and changes in membrane fluidity may alter the kinetics of transitions between conformational states (Andersen and Koeppe 2007). Cholesterol-induced modulation of membrane properties has also been suggested to affect protein function through changes in the hydrophobic bilayer thickness, membrane curvature, lipid packing density, and the lateral pressure profile (Yeagle 1991;Cantor 1999;Lee 2003 However, it must be noted that the physiologic roles of cholesterol are numerous, complex, and difficult to analyze, as cholesterol simultaneously affects many interconnected membrane material properties on both a molecular and cellular scale (Yeagle 1991;Andersen and Koeppe 2007). It may be that cells maintain plasma membrane cholesterol levels in a constant balance between opposing effects on bilayer properties and/or lateral organization within the membrane plane (Yeagle 1991;Mouritsen and Zuckermann 2004).…”

“…regulator of membrane material properties including, but not limited to, lateral mobility, permeability, stiffness, mechanical moduli, lateral membrane organization, hydrophobic thickness, and lipid packing density (Needham and Nunn 1990;Yeagle 1991;Cullis et al 1996;Mouritsen and Zuckermann 2004;McIntosh and Simon 2006;Andersen and Koeppe 2007). Recently, changes in cochlear cholesterol levels were shown to modulate the amplitude of distortion product otoacoustic emissions (DPOAEs), consistent with changes in electromotility ).…”

“…Equally important, but less examined, is the role the plasma membrane environment plays in prestin activity and OHC electromotility. The relationship between the material (i.e., chemical, physical, and mechanical) properties of biological membranes and their physiologic function is an area of growing interest, and many membrane properties affect the function of diverse membrane proteins (Yeagle 1991;Cullis et al 1996;Bastiaanse et al 1997;Lundbaek et al 2004;Janmey and Kinnunen 2006;Andersen and Koeppe 2007). As a notable recent example, changes in lipid composition and membrane tension were shown to alter the channel gating characteristics of voltage-dependent potassium channels (Schmidt and Mackinnon 2008).…”