Observation of Inhomogeneity in the Lipid Composition of Individual Nanoscale Liposomes

Liposomes are one of the most extensively used model systems for studying the physical and chemical properties of membranes and the majority of these studies have implicitly assumed that all liposomes in an ensemble are identical. However recent measurements performed at the level of single liposomes revealed the existence of intrinsic intra-sample heterogeneities that were otherwise averaged out in ensemble experiments.By employing fluorescently labeled lipids and measuring at the single liposome level we examined the compositional inhomogeneity between individual liposomes within an ensemble. In a recent publication we demonstrated an up to ten-fold variation in the relative lipid composition of individual liposomes with diameters between 50 nm and 15 μm.1 This observation is made for both a variety of different lipid-labels and compositions, which suggest that compositional inhomogeneity is a general phenomenon present in liposome systems. As a result, bulk measurement of physical and chemical properties that depend on bilayer composition, e.g. phase-transition temperature, will produce results representing the ensemble average, which will be a convolution of the properties arising from many different bilayer compositions of the individual liposomes. Furthermore, we saw that the choice of liposome preparation method greatly influences the degree of compositional inhomogeneity. This could be particularly important when using liposomes as drug delivery carriers where the monodispersity of, and control over, bilayer properties is instrumental.Since the physicochemical properties of liposomes are directly linked to their composition a direct consequence of compositional inhomogeneities is a polydispersity in the properties of the individual liposomes in an ensemble.(1) Larsen, J.; Hatzakis, N. S.; Stamou, D. J. Am. Chem. Soc. 2011, 133, 10685-10687.