Motions and interactions of phospholipid head groups at the membrane surface. 2. Simple alkyl head groups

As a reference point for comparison with more complex head groups, a set of phospholipids with simple alkyl head groups has been studied. These analogues resemble the naturally occurring phospholipids, except they have phosphomethanol, -ethanol, -1-propanol, and -1-butanol as head groups. The gel-to-liquid-crystalline phase transition temperatures were measured with differential scanning calorimetry, and the phase properties of multilamellar dispersions were examined with phosphorus-31 NMR. The effect of the head-group size was found to be rather small. These lipids were synthesized with deuterium labels incorporated into the alcohol portion at all positions in the head groups except butanol, which was labeled only in the C-1 position. Determination of the 2H residual quadrupole splittings led to an analysis of the head-group ordering properties. Specifically, these data showed that increasing the length of the head group leads to a more perpendicular orientation of the head group relative to the bilayer surface. Phosphorus-31 chemical shift anisotropy data were also compatible with this result. Measurement of surface pressure-area diagrams of monolayers of these compounds revealed that at high pressures (30 dyn/cm) all four lipids occupied similar areas (40-44 A2/molecule), yet at lower pressures, the larger the head group, the larger the occupied surface area. This result suggests that in a bilayer the fatty acyl chains occupy similar areas independent of the alkyl head-group size, and the larger head groups cannot pack properly without some conformational adjustment. The addition of phosphatidylcholine with its relatively bulky head group decreases the area available to the alkyl head groups, pushing the alkyl head groups out of the plane of the bilayer surface. Cholesterol, on the other hand, acts as a "spacer", increasing the area available to the head group, and leads to the opposite effect; i.e., the head groups can relax into a conformation more parallel to the bilayer surface. These data illustrate the types of steric effects which can be expected at the membrane surface. Dynamic properties were investigated by measurement of the 2H spin-lattice (T1) NMR relaxation times. These relaxation times could be compared with those from other parts of a phospholipid molecule, namely, the glycerol backbone and the fatty acyl chains. The rates of segmental motion in these head groups were similar to the first C-2 to C-8 segments of the fatty acyl chains, indicating considerable head-group flexibility.