The in vivo efficacy and tolerance of polyethylene glycol (PEG)-decorated drug nanocarriers, such as liposomes, is compromised by their tendency to induce the generation of PEG-specific immunoglobulin M (IgM) antibodies. Recently, a number of independent studies have reported on an attenuated anti-PEG immune response upon incorporation of gangliosides in the membrane of PEGylated liposomes. In the present study we investigate the effect of gangliosides on the self-assembled structures found in lipid dispersions based on hydrogenated egg phosphatidylcholine (HEPC), cholesterol and 1,2-distearoyl-sn-gly cero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-PEG(2000)). Results from cryo-transmission electron microscopy (cryo-TEM) and dynamic light scattering (DLS) investigations show that gangliosides promote structural transitions from liposomes to bilayer disks. In case of samples comprising 5 mol% PEG-conjugated lipids (PEG-lipid), inclusion of 2.5 mol% ganglioside (porcine ganglioside extract) results in the presence of a small but significant amount of disks. With increasing ganglioside content the population of disks grows at the expense of the liposomes. Comparative investigations using isolated ganglioside components reveal that disialoganglioside GD1a is more potent than monosialoganglioside GM1 in promoting disk formation. Experiments involving liposome encapsulated carboxyfluorescein confirm that the ganglioside-induced structural transformations have a detrimental effect on the total entrapped aqueous volume of the samples. The reported coexistence of liposomes and bilayer disks may if overlooked have important implications for the therapeutic efficacy and immunogenicity of ganglioside-supplemented liposomal formulations. (C) 2020 The Author(s). Published by Elsevier Inc.