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

Patrick Garidel,Katja Knauf,Alfred Blume,Annegret Hildebrand

doi:10.3390/12102292

Patrick Garidel, Katja Knauf + Show 2 more

Open Access

https://doi.org/10.3390/12102292

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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).

Highlights

Bile is a secretory and excretory fluid, which is secreted by the gall bladder into the intestine
Isothermal titration calorimetry (ITC) was used for the characterisation of the interaction of the bile salt detergents sodium cholate and sodium deoxycholate with model membranes
The liposomes were prepared from phosphatidylcholines (PCs) with saturated acyl chains of different length (C14: 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine, DMPC, and C16: 1,2-dipalmitoyl-sn-glycero-3phosphatidylcholine, DPPC), unsaturated fatty acids (1-palmitoyl-2-oleoyl-sn-glycero-3phosphatidylcholine, POPC) and of a natural occurring PC source composed of lipids with mainly unsaturated acyl chains

Summary

Introduction

Bile is a secretory and excretory fluid, which is secreted by the gall bladder into the intestine. There is a distribution of monomer detergent molecules (at concentrations below the cmc) between the lipid membrane phase and the bulk aqueous water phase and mixed vesicles are formed.

Results

Conclusion