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Article
Mechanism of pH-triggered collapse of phosphatidylethanolamine liposomes stabilized by an ortho ester polyethyleneglycol lipid
Biophysical Journal
  • Xin Guo, University of California, San Francisco
  • J. Andrew MacKay, University of California, San Francisco
  • Francis C. Szoka, Jr., University of California, San Francisco
Document Type
Article
DOI
http://doi.org/10.1016/S0006-3495(03)74986-8
Publication Date
3-1-2003
Abstract
The mechanism of pH-triggered destabilization of liposomes composed of a polyethyleneglycol-orthoester-distearoylglycerol lipid (POD) and phosphatidyl ethanolamine (PE) has been studied using an ANTS/DPX leakage and a lipid-mixing assay. We developed a kinetic model that relates POD hydrolysis to liposome collapse. This minimum-surface-shielding model describes the kinetics of the pH-triggered release of POD/PE liposomes. In the model, when acid-catalyzed hydrolysis lowers the mole percentage of POD on the liposome surface to a critical level, intervesicular lipid mixing is initiated, resulting in a burst of contents release. Two phases of content leakage are observed: a lag phase and a burst phase. During the lag phase, less than 20% of liposomal contents are released and the leakage begins to accelerate when approaching to the transition point. During the burst phase, the leakage rate is dependent on interbilayer contact. The burst phase occurs when the surface density of the PEG lipid is 2.3 ± 0.6 mol%, regardless of the pH. Vesicles containing 4 mol% of a pH-insensitive PEG-lipid conjugate and 10% POD did not leak contents or collapse at any pH. These data are consistent with the stalk theory to describe the lamellar-to-inverted hexagonal phase transition and set a lower bound of ∼16 PE lipids on the external monolayer as the contact site required for lipid mixing between two bilayers.
Citation Information
Xin Guo, J. Andrew MacKay and Francis C. Szoka. "Mechanism of pH-triggered collapse of phosphatidylethanolamine liposomes stabilized by an ortho ester polyethyleneglycol lipid" Biophysical Journal Vol. 84 Iss. 3 (2003) p. 1784 - 1795 ISSN: 0006-3495
Available at: http://works.bepress.com/xin-guo/24/