Janus Liposomes: Exploring Liquid-Liquid Phase-Separating Lipid Systems Alternative to DOPC/DPPC/Cholesterol

Area of Science:

• Membrane biophysics
• Colloidal materials science
• Lipid self-assembly

Background:

• Existing Janus liposome research relies heavily on a specific ternary lipid system (DOPC/DPPC/Chol).
• This limits material diversity, stability, and operational temperature range for Janus liposome production.
• Novel lipid formulations are needed to broaden applications.

Purpose of the Study:

• To systematically investigate alternative binary and ternary lipid combinations for producing microsized Janus liposomes.
• To identify new lipid systems that promote phase separation necessary for Janus liposome formation.
• To establish guidelines for designing and preparing phase-separated liposomes.

Main Methods:

• Screening of over 30 binary/ternary lipid mixtures with varying acyl chain lengths, unsaturation, and headgroup identities.
• Utilizing confocal fluorescence microscopy to identify and characterize Janus liposomes.
• Analyzing lipid composition effects on liquid-liquid phase separation.

Main Results:

• Eight novel cholesterol-containing lipid systems were identified that produce Janus liposomes in good yields.
• Cholesterol-free binary liposomes were found to undergo global liquid-liquid phase separation, albeit at lower yields.
• A set of guidelines for designing phase-separated liposomes was proposed based on experimental findings.

Conclusions:

• This study significantly expands the repertoire of lipid compositions for creating Janus liposomes.
• The findings offer new possibilities for anisotropic colloidal materials in drug delivery and active matter.
• The developed guidelines facilitate the rational design of phase-separated liposomes for diverse applications.