Pentacyclic triterpenes modulate liposome membrane fluidity and permeability depending on membrane cholesterol...

Area of Science:

• Biochemistry and Biophysics
• Membrane Biology
• Pharmacology

Background:

• Drug interactions with cell membranes are crucial for biological activity.
• Understanding how compounds like pentacyclic triterpenes (TTPs) influence membrane dynamics is essential.
• Liposomes serve as model systems to study these interactions.

Purpose of the Study:

• To investigate the effects of oleanolic acid (OA) and erythrodiol (ER), two TTPs, on liposome membrane fluidity and permeability.
• To determine how varying cholesterol content in liposomes modulates these effects.
• To correlate membrane fluidity changes with permeability alterations.

Main Methods:

• Liposomes were prepared using the reverse phase evaporation (REV) technique.
• Membrane fluidity was assessed using spin-labeled liposomes and 5- and 16-doxyl stearic acids (DSA).
• Permeability was measured by monitoring sulforhodamine B (SRB) release from TTPs-loaded liposomes and preformed vesicles at 37°C, analyzed using the Higuchi model.

Main Results:

• Erythrodiol (ER) increased membrane fluidity in the upper region, while both OA and ER induced a condensing effect in the deeper membrane regions.
• Liposome membrane composition, specifically cholesterol content, critically modulated the impact of TTPs on membrane permeability.
• A fluidizing effect on the membrane did not necessarily translate to increased membrane permeability.

Conclusions:

• Pentacyclic triterpenes exhibit distinct effects on liposome membrane fluidity depending on the region of the membrane.
• Cholesterol content is a key factor in determining how TTPs affect membrane permeability.
• The study highlights that membrane fluidization and permeabilization are independent effects, challenging previous assumptions.