Interactions of pH-sensitive peptides and polymers with lipid bilayers: Binding and membrane stability


Journal Article (Review)

The controlled release of content from liposomes is critical for their successful use as drug delivery systems. The most commonly used triggering mechanisms for content release are changes in the environment, such as a change in temperature or pH. In this case, the structure of the liposome membrane changes either by itself or by the presence of environmentally sensitive molecules, which leads to a change of membrane permeability. In this chapter we discuss the interaction of pH-sensitive molecules, such as the influenza fusion peptide mutant AcE4K and the polymer poly(2-ethylacrylic acid), with 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine membranes. We emphasize the ability of these molecules to rearrange the structure of the membrane. This ability is derived from the strength of molecular binding to the membrane interface as well as from the cohesiveness of the membrane itself. The binding of molecules to the membrane has been studied extensively; however, the coupling between binding and membrane cohesiveness is a relatively uncharted area. The binding of pH-sensitive molecules to the membrane is coupled with their protonation, whereas membrane cohesiveness depends on membrane composition. A simple model is introduced where the binding to the membrane and the work for displacing the membrane lipids and creating a vacancy for the binding molecules determine the outcome of the event. The work for creating a vacancy is dependent on membrane cohesiveness, and can be increased by adding cholesterol. The model predicts that the addition of cholesterol will increase the threshold pH for content release. The experimental data fit very well to the predictions of the model. This effect provides an opportunity for designing systems to release drugs in environments of unique pH, such as tumor tissues and endosome interiors. © 2002.

Duke Authors

Cited Authors

  • Zhelev, DV; Needham, D

Published Date

  • December 1, 2002

Published In

Volume / Issue

  • 52 /

Start / End Page

  • 437 - 464

International Standard Serial Number (ISSN)

  • 1063-5823

Citation Source

  • Scopus