Membrane lipid bilayers curvature strain

The lipid bilayer is not passive in determining membrane protein activity and function, and an accumulating body of evidence indicates that there is a coupling of membrane proteins to lipid bilayer properties. These properties include the effect of bilayer curvature strain (20), the role of specific lipids such as phosphoinositides, (21) and the effect of thickness on membrane protein function (22). The lipid composition, as well as the bilayer properties that result from this composition, act as allosteric regulators of membrane protein function. 

P SS NMR data of 14-mer amphipathic peptide (composed of leucines and phenylalanines modified by crown ethers) embedded into membranes were reported by Ouellet et al.125 The preliminary study indicated that the 14-mer peptide remains at the surface of bilayers and perturbs the lipid orientation relative to the magnetic field. 15N-31P REDOR experiments have also been used to measure the intermolecular dipole-dipole interaction between the 14-mer peptide and the PL headgroup and polar region of DMPC MLVs. The results strongly suggest that the 14-mer peptide destabilises the lipid bilayer via the induction of a positive curvature strain. 

Nonlocal bending resistance A resistance to bending resulting from the differential expansion and compression of the two adjacent leaflets of a lipid bilayer. It is termed nonlocal because the leaflets can move laterally relative to one another to relieve local strains, such that the net resistance to bending depends on the integral of the change in curvature of the entire membrane capsule. 

The entire thermodynamic system of the membrane and TM protein must be considered to understand how the protein and bilayer achieve their native state. We have summarized four of the mechanisms, hydrophobic matching, tilt angles, and specific protein/lipid and protein/protein interactions that are important in determining the stability (Fig. 5). Other important factors, such as the stability of lipid/lipid interactions, have been left out of our protein-centric view. We describe a hydrophobic mismatch as an unfavorable interaction that can be relieved by the other three processes, but we would expect all these properties of the system to interact. We could easily describe the same equilibria by saying that a strain in curvature is relieved by a hydrophobic mismatch or that strong protein/protein packing interactions might help relieve the hydrophobic mismatch or curvature stress. The complex interplay between all these interactions is at the heart of what determines membrane protein stability and will no doubt be difficult to quantify. 

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