Interaction of Bile Salts with Model Membranes Mimicking the Gastrointestinal Epithelium: A Study by Isothermal Titration Calorimetry

Abstract

Bile salts (BS) are biosurfactants synthesized in the liver and secreted into the intestinal lumen where they solubilize cholesterol and other hydrophobic compounds facilitating their gastrointestinal absorption. Partition of BS toward biomembranes is an important step in both processes. Depending on the loading of the secreted BS micelles with endogeneous cholesterol and on the amount of cholesterol from diet, this may lead to the excretion or absorption of cholesterol, from cholesterol-saturated membranes in the liver or to gastrointestinal membranes, respectively. The partition of BS toward the gastrointestinal membranes may also affect the barrier properties of those membranes affecting the permeability for hydrophobic and amphiphilic compounds. Two important parameters in the interaction of the distinct BS with biomembranes are their partition coefficient and the rate of diffusion through the membrane. Altogether, they allow the calculation of BS local concentrations in the membrane as well as their asymmetry in both membrane leaflets. The local concentration and, most importantly, its asymmetric distribution in the bilayer are a measure of induced membrane perturbation, which is expected to significantly affect its properties as a cholesterol donor and hydrophobic barrier. In this work we have characterized the partition of several BS, nonconjugated and conjugated with glycine, to large unilamellar vesicles (LUVs) in the liquid-disordered phase and with liquid-ordered/liquid-disordered phase coexistence, using isothermal titration calorimetry (ITC). The partition into the liquid-disordered bilayer was characterized by large partition coefficients and favored by enthalpy, while association with the more ordered membrane was weak and driven only by the hydrophobic effect. The trihydroxy BS partitions less efficiently toward the membranes but shows faster translocation rates, in agreement with a membrane protective effect of those BS. The rate of translocation through the more ordered membrane was faster, indicating accumulation of BS at specific locations in this membrane.

Deoxycholic acid modulates cell death signaling through changes in mitochondrial membrane properties

“…Interestingly, this effect was much less effi cient in the Chol-rich liquid-ordered phase ( l o ), possibly as a consequence of a lower affi nity of the bile acids toward more ordered membranes (14)(15)(16). This was also recently confi rmed in giant plasma membrane vesicles (GPMVs) isolated from rat tumor mast cells ( 17 ).…”

Interaction of Bile Salts With Lipid Bilayers: An Atomistic Molecular Dynamics Study

“…Membrane properties were also investigated to obtain information on the degree of perturbation induced by the different BS. The results are described and related to a recent experimental study (Coreta-Gomes et al, 2015). Differences in macroscopic membrane partition thermodynamics and translocation kinetics are rationalized in terms of the distinct structures and atomic-scale behavior of the bile salt species.…”

“…About 90% of the BS secreted into the intestine are reabsorbed. This occurs actively through the action of BS transporters (Alrefai and Gill, 2007), and through passive permeation of the unconjugated form of the BS down the concentration gradient (Donovan and Jackson, 1997; Floch, 2002; Coreta-Gomes et al, 2015).…”

Cation-sensitive compartmentalization in metallacarborane containing polymer nanoparticles

“…However, the ITC curves are comparable with a partition model employed for example for distribution of small molecules in systems exhibiting a microphase separation. [87][88][89] The saturation of the Li-based nanoparticles by K + and Na + occurred at molar ratios of 0.23 and 0.51, respectively (see leveling off of the red and black curves in Fig. 3B).…”

“…They can be clearly distinguished in the zooms of the raw heat ow curves. [86][87][88][89] In the beginning of the titration, there is only one strongly exothermic process, which is related to the cation exchange or sorption. Close to the saturation, the endotherm of simple salt mixing appears which eventually prevails.…”