Effect of headgroup on the dipole potential of phospholipid vesicles

The dipole potentials, ψ _d, of phospholipid vesicles composed of pure dimyristoylphosphatidylcholine (DMPC) or vesicles in which 50 mol% of the DMPC was substituted by dimyristoylphosphatidylserine (DMPS), dimyristoylphosphatidylglycerol (DMPG), dimyristoylethanolamine (DMPE), dimyristoylphosphatidic acid (DMPA) or monomyristoylphosphatidylcholine (MMPC) were measured via a fluorescent ratiometric method utilizing the probe di-8-ANEPPS. The PS and PG headgroups were found to cause only minor changes in ψ _d. PE caused an increase in ψ _d of 51 mV. This could be explained by a decrease in the dielectric constant of the glycerol backbone region as well as a movement of the P⁻–N⁺ dipole of the less bulky PE headgroup to a position more parallel to the membrane surface than in PC. The negatively charged PA headgroup increases ψ _d by 215 mV relative to PC alone. This indicates that the positive pole of the dipole predominantly responsible for the dipole potential is located at a position closer to the interior of the membrane than the phosphate group. The increase in the charge of the negative pole of the dipole by the phosphate group of PA increases the electrical potential drop across the lipid headgroup region. The incorporation of the single chain lipid MMPC into the membrane causes a decrease in ψ _d of 142 mV. This can be explained by a decrease in packing density within the membrane of carbonyl dipoles from the sn-2 chain of DMPC. The results presented should contribute to a better understanding of the electrical effect of lipid headgroups on the functioning of membrane proteins.