Polarity and permeation profiles in lipid membranes

Abstract

The isotropic 14 N-hyperfine coupling constant, a o N , of nitroxide spin labels is dependent on the local environmental polarity. The dependence of a o N in fluid phospholipid bilayer membranes on the C-atom position, n, of the nitroxide in the sn-2 chain of a spinlabeled diacyl glycerophospholipid therefore determines the transmembrane polarity profile. The polarity variation in phospholipid membranes, with and without equimolar cholesterol, is characterized by a sigmoidal, trough-like profile of the form {1 ؉ exp [(n ؊ no)͞]} ؊1 , where n ‫؍‬ no is the point of maximum gradient, or polarity midpoint, beyond which the free energy of permeation decreases linearly with n, on a characteristic length-scale, . Integration over this profile yields a corresponding expression for the permeability barrier to polar solutes. For fluid membranes without cholesterol, no Ϸ 8 and Ϸ 0.5-1 CH2 units, and the permeability barrier introduces an additional diffusive resistance that is equivalent to increasing the effective membrane thickness by 35-80%, depending on the lipid. For membranes containing equimolar cholesterol, n o Ϸ 9 -10, and the total change in polarity is greater than for membranes without cholesterol, increasing the permeability barrier by a factor of 2, whereas the decay length remains similar. The permeation of oxygen into fluid lipid membranes (determined by spin-label relaxation enhancements) displays a profile similar to that of the transmembrane polarity but of opposite sense. For fluid membranes without cholesterol no Ϸ 8 and Ϸ 1 CH2 units, also for oxygen. The permeation profile for polar paramagnetic ion complexes is closer to a single exponential decay, i.e., no lies outside the acyl-chain region of the membrane. These results are relevant not only to the permeation of water and polar solutes into membranes and their permeabilities, but also to depth determinations of site-specifically spin-labeled protein residues by using paramagnetic relaxation agents.T he permeation profiles of water and polar solutes into lipid membranes are fundamental not only to transport studies but also to the energetics of insertion of proteins into membranes. Additionally, the permeation profiles of paramagnetic relaxation agents are of practical importance for depth determinations in membranes by site-directed spin labeling (1). Trough-like polarity profiles across lipid membranes have been established by measuring isotropic 14 N-hyperfine splitting constants, a o N , or the principal hyperfine tensor element, A zz , in lipid membranes (2-4). These are probably determined to a large extent by the penetration of water into the hydrophobic interior. This will modulate the energetics of burying amino acid residues in membranes, but has largely been neglected in favor of a uniform hydrophobic effect when analyzing the stability of integral membrane proteins (e.g., ref 5). White and Wimley (6) are among the few authors who have addressed this problem specifically. Interestingly, experiments on paramagnetic enhancements of spin l...

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