Membranolytic Activity of Bile Salts: Influence of Biological Membrane Properties and Composition

Abstract

Abstract:The two main steps of the membranolytic activity of detergents: 1) the partitioning of detergent molecules in the membrane and 2) the solubilisation of the membrane are systematically investigated. The interactions of two bile salt molecules, sodium cholate (NaC) and sodium deoxycholate (NaDC) with biological phospholipid model membranes are considered. The membranolytic activity is analysed as a function of the hydrophobicity of the bile salt, ionic strength, temperature, membrane phase properties, membrane surface charge and composition of the acyl chains of the lipids. The results are derived from calorimetric measurements (ITC, isothermal titration calorimetry). A thermodynamic model is described, taking into consideration electrostatic interactions, which is used for the calculation of the partition coefficient as well as to derive the complete thermodynamic parameters describing the interaction of detergents with biological membranes (change in enthalpy, change in free energy, change in entropy etc). The solubilisation properties are described in a so-called vesicle-to-micelle phase transition diagram. The obtained results are supplemented and confirmed by data obtained from other biophysical techniques (DSC differential scanning calorimetry, DLS dynamic light scattering, SANS small angle neutron scattering).

Membrane solubilisation and reconstitution by octylglucoside: Comparison of synthetic lipid and natural lipid extract by isothermal titration calorimetry

“…Hence, composition-dependent transformations of vesicles into micelles (solubilisation) or vice versa (reconstitution) in mixtures of bilayer-forming phospholipids and micelle-forming detergents have received particular attention. The most thoroughly studied detergents include n-octyl-β-D-glucopyranoside (octylglucoside, OG; [2][3][4][5][6]), Triton X-100 [3,7], 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulphonate (CHAPS; [8][9][10]), and other bile acid derivatives [3][4][5]11,12].…”

Curcumin-loaded mixed micelles: preparation, optimization, physicochemical properties and cytotoxicityin vitro

“…For organism, bile salts, secreted by liver and stored in the gall bladder, could form a kind of stable mixed micellar system with PCs, glycerides and fatty acids during lipid digestion in the small intestine Duan et al, 2011). The bile salt/PC micelles can package cholesterol inside the hydrophobic core, and the solubility, stability and bioavailability of poorly water-soluble drugs could be enhanced in the same way (Dangi et al, 1995;Garidel et al, 2007). Meanwhile, water-soluble drugs would insert into the hydrophilic palisade layer of micelles to separate from the surrounding unavailable environment.…”

Bile Acid Administration Elicits an Intestinal Antimicrobial Program and Reduces the Bacterial Burden in Two Mouse Models of Enteric Infection

“…Due to their detergent nature and membranolytic activity (8), bile acids are microbicidal (9, 10), a feature considered important for limiting the growth of bacteria in the proximal small intestine (10,11). However, recent evidence suggests that in addition to that, bile acid signaling to the gut epithelium is important for intestinal immunity and homeostasis, as genetic deficiency of the bile acid nuclear receptor FXR (farnesoid X receptor) facilitates intestinal bacterial overgrowth and leads to a compromised intestinal barrier (12).…”