Interaction of hexadecylbetainate chloride with biological relevant lipids.

The present work investigates the interaction of hexadecylbetainate chloride (C(16)BC), a glycine betaine-based ester with palmitoyl-oleoyl-phosphatidylcholine (POPC), sphingomyelin (SM), and cholesterol (CHOL), three biological relevant lipids present in the outer leaflet of the mammalian plasma membrane. The binding affinity and the mixing behavior between the lipids and C(16)BC are discussed based on experimental (isothermal titration calorimetry (ITC) and Langmuir film balance) and molecular modeling studies. The results show that the interaction between C(16)BC and each lipid is thermodynamically favorable and does not affect the integrity of the lipid vesicles. The primary adsorption of C(16)BC into the lipid film is mainly governed by a hydrophobic effect. Once C(16)BC is inserted in the lipid film, the polar component of the interaction energy between C(16)BC and the lipid becomes predominant. Presence of CHOL increases the affinity of C(16)BC for membrane. This result can be explained by the optimal matching between C(16)BC and CHOL within the film rather by a change of membrane fluidity due to the presence of CHOL. The interaction between C(16)BC and SM is also favorable and gives rise to highly stable monolayers probably due to hydrogen bonds between their hydrophilic groups. The interaction of C(16)BC with POPC is less favorable but does not destabilize the mixed monolayer from a thermodynamic point of view. Interestingly, for all the monolayers investigated, the exclusion surface pressures are above the presumed lateral pressure of the plasma membranes suggesting that C(16)BC would be able to penetrate into mammalian plasma membranes in vivo. These results may serve as a useful basis in understanding the interaction of C(16)BC with real membranes.

Penetration behaviour of alkylbetainate chlorides into lipid monolayers.

In this paper, the penetration behaviour of the alkylbetainate chloride surfactants (C(n)BC, n=10-16) into lipid monolayers of dipalmitoylphosphatidylserine (DPPS), dipalmitoylphosphatidic acid (DPPA), dipalmitoylphosphatidylethanolamine (DPPE), palmitoyoleoylphosphatidylcholine (POPC) and cholesterol (CHOL) is investigated using the Langmuir trough technique. The penetration of C(n)BC is followed by measurement of the surface pressure increase (Δπ) at a constant surface area after the injection of C(n)BC into the aqueous phase, underneath the lipid monolayer previously spread at the air-water interface at 25°C and at different initial surface pressures (π(i)). The influence of both the lipid head group and the surfactant hydrocarbon chain length on the effectiveness of C(n)BC penetration into these monolayers is discussed. The results have shown that C(n)BC adsorb at the air-water interface giving evidence of their surface-active properties. The adsorption kinetics of C16BC into different lipid monolayers are lipid head charge and lipid head volume-dependent. The magnitude of the surface pressure increase (Δπ) arises in the following order: DPPA>DPPS≫CHOL≈DPPE>POPC. C(n)BC penetration into negatively-charged (DPPS and DPPA) monolayers does not seem to depend on surfactant alkyl-chain length compared to uncharged (CHOL) and zwitterionic (DPPE and POPC) monolayers for which Δπ increases with a larger alkyl-chain length. Electrostatic interactions are mainly involved in the affinity of C(n)BC with monolayers but the hydrophobic effect plays also a role.