Understanding the Enhanced Magnetic Response of Aminocholesterol Doped Lanthanide-Ion-Chelating Phospholipid Bicelles

Abstract

Cholesterol (Chol-OH) and its conjugates are powerful molecules for engineering the physicochemical and magnetic properties of phospholipid bilayers in bicelles. Introduction of aminocholesterol (3β-amino-5-cholestene, Chol-NH) in bicelles composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and the thulium-ion-chelating phospholipid 1,2-dimyristoyl-sn-glycero-3-phospho-ethanolamine-diethylene triaminepentaacetate (DMPE-DTPA/Tm) results in unprecedented high magnetic alignments by selectively tuning the magnetic susceptibility Δχ of the bilayer. However, little is known on the underlying mechanisms behind the magnetic response and, more generally, on the physicochemical forces governing a Chol-NH doped DMPC bilayer. We tackled this shortcoming with a multiscale bottom-up comparative investigation of Chol-OH and Chol-NH mixed with DMPC. First, simplified monolayer models on a Langmuir trough were employed to compare the two steroid molecules at various contents in DMPC. In a second step, a molecular dynamics (MD) simulation allowed for a more representative model of the bicelle bilayer while monitoring the amphiphiles and their interactions on the molecular level. In a final step, we moved away from the models and investigated the effect of temperature on the structure and magnetic alignment of Chol-NH doped bicelles by SANS. The DMPC/steroid monolayer studies showed that Chol-OH induces a larger condensation effect than Chol-NH at steroid contents of 16 and 20 mol %. However, this tendency was inversed at steroid contents of 10, 30, and 40 mol %. Although the MD simulation with 16 mol % steroid revealed that both compounds induce a liquid-ordered state in DMPC, the bilayer containing Chol-NH was much less ordered than the analogous system containing Chol-OH. Chol-NH underwent significantly more hydrogen bonding interactions with neighboring DMPC lipids than Chol-OH. It seems that, by altering the dynamics of the hydrophilic environment of the bicelle, Chol-NH changes the crystal field and angle of the phospholipid-lanthanide DMPE-DTPA/Tm complex. These parameters largely determine the magnetic susceptibility Δχ of the complex, explaining the SANS results, which show significant differences in magnetic alignment of the steroid doped bicelles. Highly magnetically alignable DMPC/Chol-NH/DMPE-DTPA/Tm (molar ratio 16:4:5:5) bicelles were achieved up to temperatures of 35 °C before a thermoreversible rearrangement into nonalignable vesicles occurred. The results confirm the potential of Chol-NH doped bicelles to act as building blocks for the development of the magnetically responsive soft materials of tomorrow.

Development of Smart Optical Gels with Highly Magnetically Responsive Bicelles

“…For example, the peak in birefringence observed at 26 °C on heating could be caused by the appearance of a concentric hole in the bicelles, as previously reported in steroid-doped assemblies. 21,35,36,38,40 The bicelle alignment was not altered in this temperature range, as the A f values remained constant (see Figure 1). The birefringence signal remained unchanged when the magnetic field was ramped down to 0 T at 4 °C.…”

“…38 The liquid ordered phase induced by the presence of the steroid molecule gives rise to the thermal resistance of the bicelles. 29,35,38,49,50 These systems are alignable above the gelling temperature of porcine gelatin of 22 °C on cooling at 1 °C/min. Therefore, the bicelles may be entrapped in an aligned state in the gelatin network, fulfilling the requirements for delivering optical properties to the gel.…”

“…Bicelles with an average hydrodynamic diameter D H of 134 ± 23 nm were obtained, in line with previous findings. 35,37,38 Porcine gelatin [10% (w/w)] was subsequently dissolved in the bicelle solution at 60 °C, and the sample was stored in a gelled state at 5 °C before the measurement. The magnetic alignment of the bicelles as a function of temperature was evaluated through computation of alignment factors A f in SANS at 8 T, and the resulting optical properties were monitored by birefringence at 5.5 T.…”

“…The alignment factor A f was computed from the 2D scattering pattern of the sample in the q-range of 0.3−0.4 nm −1 to quantify the magnetic alignment of the samples, as described previously. 20,21,[35][36][37][38]40,41 A f is the second cosine Fourier coefficient of the normalized azimuthal scattering intensity I(φ)…”

“…37 Moreover, the steroid moiety generates a liquid-ordered state in the phospholipid bilayer, enabling the magnetically alignable bicelles to exist at temperatures as high as 35 °C instead of 21 °C observed in pure DMPC-based bicelles. 21,36,38 The possibility of generating optical gels with this novel bicelle system was demonstrated and further investigated by small-angle neutron scattering (SANS) and birefringence measurements. In the second step, the magnetic response of the DMPC/Chol-NH 2 /DMPE-DTPA/Ln 3+ (molar ratio 16:4:5:5) bicelles was greatly enhanced with optimized fabrication procedures.…”