The intrinsic structural asymmetry of highly curved phospholipid bilayer membranes

Phosphorus-31 NMR studies of solutions of small l-α-dipalmitoyl phosphatidylcholine bilayer vesicles containing sodium dimethyl phosphate uniformly distributed between the continuous external and the intravesicular aqueous spaces, with the paramagnetic shift reagent Pr³⁺ present only in the external space, are reported. These studies give the distribution both of dipalmitoyl phosphatidylcholine in the vesicle inner and outer monolayers and of dimethyl phosphate in the aqueous spaes. With the third necessary parameter obtained from the vesicle sedimentation coefficient, the very different packing parameters of dipalmitoyl phosphatidylcholine in inner and outer monolayers can be determined. The vesicle outer radius is 109 Å. Although the total bilayer thickness is virtually identical to that of planar bilayers, the outer monolayer is thicker (20 Å) and the inner monolayer thinner (15 Å). The area per head group at the inner surface, 68 Ų, is like the planar value, but the tails are much more folded, so as to decrease the radial lengths and increase the tangential spread (to 94 Ų). The reverse is true in the outer layer: the surface per head group is 76 Ų, tapering to 51 Ų in the tail region, so that outer layer tails are relatively extended. The difference is equivalent to a shift of about two 2g1 kinks from outer to inner layers; the uneven packing certainly affects fluidity, and may have important biological consequences.