Effects of N,N-dimethyl-N-alkylamine-N-oxides on DOPC bilayers in unilamellar vesicles: small-angle neutron scattering study

Abstract

Small-angle neutron scattering data were collected from aqueous dispersions of unilamellar vesicles (ULVs) consisting of mixtures of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine and a homologous series of N,N-dimethyl-N-alkylamine-N-oxides (CnNO, n = 12, 14, 16, and 18, where n is the number of carbon atoms in the alkyl chain). A modeling approach was applied to the neutron scattering curves to obtain the bilayer structural parameters. Particularly, the external (2)H2O/H2O contrast variation technique was carried out on pure dioleoylphosphatidylcholine (DOPC) ULVs to determine the hydrophilic region thickness [Formula: see text] = 9.8 ± 0.6 Å. Consequently, the hydrocarbon region thickness [Formula: see text], the lateral bilayer area per one lipid molecule [Formula: see text], and the number of water molecules located in the hydrophilic region per one lipid molecule [Formula: see text] were obtained from single-contrast neutron scattering curves using the previously determined [Formula: see text]. The structural parameters were extracted as functions of [Formula: see text] (the CnNO:DOPC molar ratio) and n. The dependences [Formula: see text] provided the partial lateral areas of CnNOs ([Formula: see text]) and DOPC ([Formula: see text]) in bilayers. It was observed that the [Formula: see text]'s were constant in the investigated interval of [Formula: see text] and for n = 12, 14, and 16 equal to 36.6 ± 0.4 Å(2), while [Formula: see text] increased to 39.4 ± 0.4 Å(2). The bilayer hydrocarbon region thickness [Formula: see text] decreased with intercalation of each CnNO. This effect increased with [Formula: see text] and decreased with increasing CnNO alkyl chain length. The intercalation of C18NO changed the [Formula: see text] only slightly. To quantify the effect of CnNO intercalation into DOPC bilayers we fit the [Formula: see text] dependences with weighted linear approximations and acquired their slopes [Formula: see text].

Neutrons in studies of phospholipid bilayers and bilayer–drug interaction. II. Small-angle scattering

“…As suggested by Balgavý & Devínsky (1996), the cut-off effects -a quasi-parabolic dependence are primarily caused by a combination of partition equilibria and elimination of free volume below the hydrophobic substituents, which are usually shorter than phospholipid hydrocarbon chains in biomembranes. This hypothesis was recently confirmed in the paper by Belička et al (2014b). As in the above-described publication with alkanols, it was demonstrated by means of SANS on unilamellar liposomes of DOPC that at the same concentration of amphiphilic CnNOs, the size of a defect underlying the changes in the bilayer varies in accordance with the trends predicted in the paper by Balgavý & Devínsky (1996).…”

Lipid based drug delivery systems: Kinetics by SANS

“…These defects, eliminated by chain bending, lead to a decrease of the thickness (d C ) of the hydrophobic region [14,32]. In our previous work [15] we found that the thickness of the hydrophobic region of dioleoylphosphatidylcholine (DOPC) bilayer (d C =27.4±0.1 Å) decreases to d C = 24.9 Å, and the area per 1 molecule increases from A = 70.4 Å 2 (for DOPC) up to A= 106.6 Å 2 at C 12 NO:DOPC=1 mol/mol. The polar head group of phosphatidylethanolamines is smaller in comparison to that bulky in phosphatidylcholines and also the headgroup region is thinner.…”

“…Figure 3 shows SANS curves of C 12 NO/DOPE vesicles and a mixture of DNA -C 12 NO/DOPE, at neutral pH. In spite the fact that C 12 NO/DOPE dispersion was extruded prior to measurements, the curves do not show the typical profile of scattering of unilamellar vesicles like we observed for example in [15]. Due to rapid aggregation, the dispersions are formed by oligolamellar up to multilamellar vesicles.…”

“…C 12 NO is widely used in pharmaceutical and cosmetic formulations, as detergent in household dish washing liquids and surface cleaners and in various areas of industry [9,10]. An amphiphile C 12 NO incorporates into the biological membrane and can induce changes of fluidity [11], and thickness [12][13][14][15] of lipid bilayers. At high concentration C 12 NO destabilizes lipid bilayers forming non-lamellar phases or mixed micelles [16].…”

Stimuli responsive polymorphism of C12NO/DOPE/DNA complexes: Effect of pH, temperature and composition

“…C 12 NO as an amphiphile incorporates into biological membranes and can induce changes of fluidity [24,25] and thickness [26][27][28][29] of lipid bilayers. At high concentration, C 12 NO destabilizes lipid bilayers, and forms non-bilayer phases and mixed micelles [30,31].…”