LUV's lipid composition modulates diffusion of bile acids.

Area of Science:

• Biochemistry
• Membrane Biophysics
• Lipid Bilayer Dynamics

Background:

• Bile acids are crucial for digestion and signaling.
• Understanding their membrane interactions is key to cellular processes.
• Model membranes provide insights into complex biological systems.

Purpose of the Study:

• To investigate the diffusion of lithocholic acid (LCA) and chenodeoxycholic acid (CDCA) across lipid vesicles.
• To determine how membrane lipid composition affects bile acid permeability and fluidity.
• To explore the relationship between bile acid hydrophobicity, aggregation, and membrane transport.

Main Methods:

• Preparation of large unilamellar vesicles (LUVETs) using phosphatidylcholine, sphingomyelin, cholesterol, and cardiolipin.
• Pyranine fluorescence method to measure bile acid diffusion.
• Carboxyfluoresceine (CF) inclusion assay for membrane permeability.
• Diphenylhexatriene (DPH) and TMA-DPH probes for membrane fluidity assessment.

Main Results:

• CDCA showed higher penetration into sphingomyelin-containing vesicles compared to LCA.
• LCA demonstrated better penetration into cholesterol-containing vesicles.
• Cardiolipin influenced CDCA diffusion more than LCA diffusion.
• Membrane fluidity and permeability were modulated by bile acid interactions.

Conclusions:

• Bile acid diffusion across model membranes is influenced by both hydrophobicity and membrane lipid composition.
• Bile acid aggregation states and conformational forms may play a significant role in membrane transport.
• Lipid composition, including sphingomyelin, cholesterol, and cardiolipin, differentially affects bile acid permeability.