The Effect of Methylated Lithocholic Acid on Plasma Membrane Properties: The Difference with the Effect of Cholesterol

Abstract Bile acids form micelles that are essential for absorbing dietary lipids. However, excessive amounts of bile acid micelles may disrupt the plasma membrane by removing phospholipids, resulting in cell death. We hypothesized that the bent geometrical structure of the steroid scaffold of bile acids decreases lipid order (similar to unsaturated phospholipids with cis double bonds), disrupting the plasma membrane. Here, lithocholic acid (LCA), a bile acid, was methylated to prevent micellization. Methylated lithocholic acid (Me-LCA) was mixed with a thin phase-separated lipid layer comprising 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and cholesterol (Chol). Me-LCA was localized not in the gel phase but in the liquid crystalline phase and excess Me-LCA did not affect phase separation. Me-LCA was distributed in the plasma membrane and the organelle membranes. However, the Me-LCA did not affect the membrane properties, membrane fluidity, and hydrophobicity of liposomes composed of DOPC, DPPC and Chol, and it did not affect proliferation. These results suggest that the removal of phospholipids from the plasma membrane by bile acid micelles mainly contributes to cell death.