Headgroup hydration and mobility of DOTAP/DOPC bilayers: a fluorescence solvent relaxation study

Area of Science:

• Biophysics
• Materials Science
• Biochemistry

Background:

• Liposome surface properties are vital for interactions with macromolecules.
• Cationic liposomes are widely used for gene delivery applications.
• Understanding lipid bilayer structure and dynamics is key to optimizing liposome function.

Purpose of the Study:

• To investigate the structural and dynamic changes in lipid bilayers composed of cationic dioleoyltrimethylammoniumpropane (DOTAP) and neutral dioleoylphosphatidylcholine (DOPC).
• To probe the effects of varying DOTAP concentrations on lipid headgroup interactions and water penetration.
• To elucidate the role of biophysical properties in liposome-mediated gene delivery.

Main Methods:

• Fluorescence solvent relaxation technique using naphthalene derivatives (Patman, Laurdan, Prodan) as fluorescent probes.
• Wavelength-dependent parallax quenching to determine dye locations within the bilayer.
• Acrylamide quenching experiments to study DOTAP-induced dye relocalization and solvent dynamics.

Main Results:

• Precise localization of Laurdan and Patman dyes within the dioleoylphosphatidylcholine (DOPC) bilayer was determined.
• Nonmonotonic dependence of dipolar relaxation kinetics on DOTAP content was observed, with a maximum mean solvent relaxation time at 30 mol % DOTAP.
• DOTAP addition up to 30% increased phospholipid headgroup packing without affecting bound water at sn(1) carbonyls; higher concentrations led to increased water penetration.

Conclusions:

• Lipid bilayer structure and dynamics are significantly modulated by the concentration of cationic lipids like DOTAP.
• A specific concentration of DOTAP (30 mol %) optimizes lipid headgroup packing, influencing membrane properties.
• Altered water penetration at higher DOTAP concentrations may affect the efficacy and stability of cationic liposomes in gene delivery systems.