Bipolar Imidazolium-Based Lipid Analogues for Artificial Archaeosomes

Area of Science:

• Biochemistry
• Materials Science
• Biophysics

Background:

• Archaeal lipids are of interest for biomedical applications due to their stable membrane properties.
• Chemical synthesis offers a viable route to produce archaeal lipid analogues when isolation is challenging.

Purpose of the Study:

• To synthesize and characterize novel bipolar alkylated imidazolium salts (bolalipid analogues) with varying chain lengths.
• To investigate the structural and phase behavior of these synthetic bolalipids and their mixtures with phospholipid model membranes.
• To explore the potential of these analogues in mimicking archaeal lipid behavior and modifying membrane properties.

Main Methods:

• Synthesis of bipolar alkylated imidazolium salts (BIm10-32).
• Differential scanning calorimetry (DSC), fluorescence and FTIR spectroscopy.
• Confocal fluorescence microscopy, dynamic light scattering (DLS), small-angle X-ray scattering (SAXS), and transmission electron microscopy (TEM).

Main Results:

• Long-chain BImN32 formed monolayer sheets and integrated into phospholipid membranes, exhibiting a fluidizing effect.
• BImN32 incorporation increased lipid packing in DPPC liposomes, enhancing thermal stability and high-pressure resistance.
• BImN32 modified lateral membrane organization, topology, and fusogenicity in anionic model biomembranes.

Conclusions:

• Long-chain imidazolium-based bolalipid analogues can adjust membrane biophysical properties and facilitate electrostatic interactions.
• These synthetic lipids offer a tractable approach for designing extremophilic liposomes for drug and vaccine delivery.