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Structural characterization of novel cationic diC16-amidine bilayers: Evidence for partial interdigitation
Biochimica Et Biophysica Acta
|October 16, 2014
Summary
Novel cationic lipid diC16-amidine forms a partially interdigitated gel phase, enhancing its fusion activity at physiological temperatures for potential delivery applications.
Area of Science:
- Lipid bilayer biophysics
- Membrane biophysics
- Materials science
Background:
- Cationic lipids are crucial for drug and gene delivery systems.
- Understanding lipid bilayer structure and dynamics is key to optimizing delivery vehicles.
- Dipalmitoyl phosphatidylcholine (DPPC) serves as a benchmark zwitterionic lipid with a known bilayer structure.
Purpose of the Study:
- To compare the bilayer structure and properties of a novel cationic lipid, diC16-amidine, with the zwitterionic lipid DPPC.
- To investigate the impact of diC16-amidine's unique structure on its phase behavior and fusogenic activity.
- To assess the potential of diC16-amidine for delivery applications.
Main Methods:
- Differential scanning calorimetry (DSC) to analyze phase transition temperatures and cooperativity.
- Electron spin resonance (ESR) spectroscopy using various spin labels (PCSL) to probe lipid tail order and flexibility.
- Fluorescence resonance energy transfer (FRET) assays to evaluate fusogenic activity.
Main Results:
- diC16-amidine and DPPC bilayers exhibit similar phase transition temperatures, but diC16-amidine shows less cooperative transitions and no pretransition.
- ESR data indicate a partially interdigitated gel phase for diC16-amidine, with rigidification of the 14th and 16th carbons.
- The lamellar fluid phase of diC16-amidine is more rigid than DPPC, and its fusogenic activity is higher in the gel phase.
Conclusions:
- diC16-amidine forms a unique partially interdigitated gel phase structure.
- This interdigitated structure is crucial for enhanced fusogenic activity.
- With a gel-fluid transition temperature of 42°C, diC16-amidine is fusogenic at physiological temperatures, making it a promising candidate for delivery applications without helper lipids.
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