Structural characterization of cationic DODAB bilayers containing C24:1 β-glucosylceramide

Area of Science:

• Membrane biophysics
• Lipid self-assembly
• Materials science

Background:

• Cationic lipids like DODAB are crucial for drug/vaccine delivery systems.
• Understanding lipid-bilayer structural changes is key to optimizing formulation.
• β-glucosylceramides (βGlcCer) are bioactive lipids with potential applications.

Purpose of the Study:

• To investigate the structural impact of incorporating C24:1 β-glucosylceramide (βGlcCer) into cationic DODAB bilayers.
• To determine the miscibility and phase behavior of βGlcCer-DODAB mixtures.
• To assess the potential of these mixed membranes for applications like vaccine adjuvants.

Main Methods:

• Differential Scanning Calorimetry (DSC) to analyze phase transitions.
• Electron Spin Resonance (ESR) spectroscopy to probe membrane dynamics and order.
• Fluorescence microscopy to assess lipid miscibility and domain formation.

Main Results:

• C24:1 βGlcCer is fully miscible with DODAB across tested concentrations, with no phase separation observed.
• βGlcCer destabilizes the DODAB gel phase by reducing molecular packing, lowering transition temperature and cooperativity.
• Incorporation of βGlcCer increases the order and rigidity of the DODAB fluid phase.

Conclusions:

• C24:1 βGlcCer incorporation significantly alters DODAB bilayer structure, loosening gel phase packing and increasing fluid phase order.
• The observed structural effects are comparable to those induced by cholesterol in DODAB bilayers.
• Characterizing cationic lipid-glucosylceramide membranes is vital for developing advanced immunotherapeutic tools, including vaccine adjuvants.