Liposomes, Disks, and Spherical Micelles: Aggregate Structure in Mixtures of Gel Phase Phosphatidylcholines and Poly(Ethylene Glycol)-Phospholipids

• Published in: Biophysical journal Vol. 85; no. 6; pp. 3839 - 3847
• Main Authors: Johnsson, Markus, Edwards, Katarina
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2003; Biophysical Society
• Subjects: Antifreeze solutions; Biophysical Phenomena; Biophysics; Cryoelectron Microscopy; Disks; Drug Delivery Systems; Drugs; Electron Spin Resonance Spectroscopy; Light; Lipid Bilayers; Lipids; Lipids - chemistry; Liposomes - chemistry; Liposomes - metabolism; Membranes; Micelles; Microscopy, Electron; Models, Biological; Molecules; Phosphatidylcholines - chemistry; Phospholipids - chemistry; Polyethylene Glycols - chemistry; Scattering, Radiation; Temperature
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1016/S0006-3495(03)74798-5

Poly(ethylene glycol) (PEG) decorated lipid bilayers are widely used in biomembrane and pharmaceutical research. The success of PEG-lipid stabilized liposomes in drug delivery is one of the key factors for the interest in these polymer/lipid systems. From a more fundamental point of view, it is essential to understand the effect of the surface grafted polymers on the physical-chemical properties of the lipid bilayer. Herein we have used cryo-transmission electron microscopy and dynamic light scattering to characterize the aggregate structure and phase behavior of mixtures of PEG-lipids and distearoylphosphatidylcholine or dipalmitoylphosphatidylcholine. The PEG-lipids contain PEG of molecular weight 2000 or 5000. We show that the transition from a dispersed lamellar phase (liposomes) to a micellar phase consisting of small spherical micelles occurs via the formation of small discoidal micelles. The onset of disk formation already takes place at low PEG-lipid concentrations (<5 mol %) and the size of the disks decreases as more PEG-lipid is added to the lipid mixture. We show that the results from cryo-transmission electron microscopy correlate well with those obtained from dynamic light scattering and that the disks are well described by an ideal disk model. Increasing the temperature, from 25°C to above the gel-to-liquid crystalline phase transition temperature for the respective lipid mixtures, has a relatively small effect on the aggregate structure.