Morphology-Induced Defects Enhance Lipid Transfer Rates

Area of Science:

• Nanoparticle science
• Physical chemistry
• Biophysics

Background:

• Interparticle molecular transfer is crucial for nanoparticle stability.
• Discoidal bicelles exhibit significantly different spontaneous lipid transfer rates compared to spherical unilamellar vesicles (ULVs).

Purpose of the Study:

• To investigate the mechanism behind the discrepancy in lipid transfer rates between discoidal bicelles and ULVs.
• To elucidate the role of bicelle structure and lipid composition in molecular transfer.

Main Methods:

• Thermodynamic analysis of lipid transfer kinetics.
• Molecular dynamics simulations to probe lipid dissociation energy.
• Investigation of factors including bicelle size and lipid chain length.

Main Results:

• Lipid transfer is entropically favorable but enthalpically unfavorable, with activation energy independent of bicelle size and lipid ratio.
• Molecular dynamics simulations identified interfacial defects in bicelles, absent in ULVs, due to lipid segregation.
• These defects lower the energy cost for lipid dissociation, facilitating transfer.

Conclusions:

• Enhanced lipid transfer in bicelles is attributed to interfacial defects arising from hydrophobic mismatch between long- and short-chain lipids.
• The observed lipid transfer rate is independent of nanoparticle stability.
• Understanding these mechanisms is key for designing stable nanoparticle systems.