Spontaneous interbilayer transfer of phospholipids: dependence on acyl chain composition

The diffusion-mediated intervesicle transfer of a variety of fluorescent N-(S-bimanylmercaptosuccinyl)phosphatidylethanolamines (BMS-PEs), and of a more limited series of radiolabeled phosphatidylcholines (PCs), has been investigated as a function of the acyl chain composition of the labeled molecules and the composition of the lipid vesicles. Increasing the total acyl chain length of a BMS-PE by two methylene residues increases the free energy of activation for probe desorption from a lipid bilayer (delta Gd not equal to) by ca. 1300 cal mol-1, while the addition of one double bond to either chain decreases delta Gd not equal to by a slightly smaller increment. The values of these increments in delta Gd not equal to are surprisingly consistent with variations in BMS-PE acyl chain length, positional isomerism (for heteroacyl BMS-PEs), and the sterol content or degree of acyl chain saturation of the lipid bilayer. However, the successive addition of multiple cis double bonds to the same acyl chain leads to progressively smaller decrements in the value of delta Gd not equal to. Radiolabeled PCs show somewhat lower absolute rates of interbilayer transfer than the corresponding BMS-PEs, but the incremental contributions of added methylene groups or cis double bonds to delta Gd not equal to are essentially identical for the two classes of lipids, validating the use of BMS-PEs as representative probes of phospholipid behavior for these experiments. Our data suggest that the relative rates of spontaneous transfer of a variety of phospholipids from bilayer membranes can be predicted to good approximation from a few basic features of the phospholipid structure.(ABSTRACT TRUNCATED AT 250 WORDS)