Liposomes, disks, and spherical micelles: aggregate structure in mixtures of gel phase phosphatidylcholines and poly(ethylene glycol)-phospholipids

Biophys J. 2003 Dec;85(6):3839-47. doi: 10.1016/S0006-3495(03)74798-5.

Abstract

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 degrees 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biophysical Phenomena
  • Biophysics
  • Cryoelectron Microscopy
  • Drug Delivery Systems
  • Electron Spin Resonance Spectroscopy
  • Light
  • Lipid Bilayers
  • Lipids / chemistry
  • Liposomes / chemistry*
  • Liposomes / metabolism
  • Micelles*
  • Microscopy, Electron
  • Models, Biological
  • Phosphatidylcholines / chemistry*
  • Phospholipids / chemistry*
  • Polyethylene Glycols / chemistry*
  • Scattering, Radiation
  • Temperature

Substances

  • Lipid Bilayers
  • Lipids
  • Liposomes
  • Micelles
  • Phosphatidylcholines
  • Phospholipids
  • Polyethylene Glycols