A Matrix Effect in Mixed Phospholipid/Fatty Acid Vesicle Formation

Abstract

The formation of mixed phospholipid/fatty acid vesicles has been studied using a combination of kinetic and structural methods. In particular, the process of spontaneous formation of vesicles on addition of oleate micelles to pre-existing POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) vesicles has been followed by turbidity−time curves, and the size and nature of the resulting structures have been determined using dynamic light scattering and electron microscopy. There is clear evidence for the operation of a POPC vesicle matrix effect in these systems. This leads to rapid formation of vesicle aggregates and control over the final size distribution such that the mixed systems are more monodisperse than in the absence of the matrix. When the molar ratio of oleic acid + oleate to phospholipid is small (up to ∼1), then the oleic acid/oleate is believed to be incorporated into the already existing vesicles with some swelling of the vesicles. At higher ratios, the behavior is more complicated, but their appears to be an increase in both the size and the number of mixed vesicles. At very large ratios ([oleic acid + oleate]/[POPC] ≈ 1000), there is still a very significant kinetic effect, coupled with the formation of multilamellar vesicles. A simple mathematical treatment is proposed, which establishes an appropriate theoretical framework for the interpretation of the results.