Single-molecule methods for monitoring changes in bilayer elastic properties.
Membrane-spanning proteins perturb the organization and dynamics of the adjacent bilayer lipids. For example, when the hydrophobic length (l) of a bilayer-spanning protein differs from the average thickness (d0) of the host bilayer, the bilayer thickness will vary locally in the vicinity of the protein in order to "match" the length of the protein's hydrophobic exterior to the thickness of the bilayer hydrophobic core. Such bilayer deformations incur an energetic cost, the bilayer deformation energy (DeltaG0def), which will vary as a function of the protein shape, the protein-bilayer hydrophobic mismatch (d0 - l), the lipid bilayer elastic properties, and the lipid intrinsic curvature (c0). Thus, if the membrane protein conformational changes underlying protein function involve the protein/bilayer interface, the ensuing changes in DeltaG0def (DeltaDeltaG0def) will contribute to the overall free-energy change of the conformational changes (DeltaG0tot)-meaning that the host lipid bilayer will modulate protein function. For a given protein, (DeltaDeltaG0def) varies as a function of the bilayer geometric properties (thickness and intrinsic curvature) and the elastic (bending and compression) moduli, which vary as a function of changes in lipid composition or with the adsorption of amphiphiles at the bilayer/solution interface. To understand how changes in bilayer properties modulate the function of bilayer-spanning proteins, single-molecule methods have been developed to probe changes in bilayer elastic properties using gramicidins as molecular force transducers. Different approaches to measuring the deformation energy are described: (1) measurements of changes in channel lifetimes and appearance rates as the lipid bilayer thickness or channel length are varied, (2) measurements of the equilibrium distribution among channels of different lengths, formed by homo- and heterodimers between gramicidin subunits of different lengths, and (3) measurements of the ratio of the appearance rates of heterodimer channels relative to parent homodimer channels formed by gramicidin subunits of different lengths.
Andersen
Olaf S
OS
Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, NY, USA.
Bruno
Michael J
MJ
Sun
Haiyan
H
Koeppe
Roger E
RE
D019281:Dimerization; D004548:Elasticity; D006096:Gramicidin / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D007473:Ion Channels / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008956:Models, Chemical; D013816:Thermodynamics
D007473:Ion Channels; D008051:Lipid Bilayers; D006096:Gramicidin