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.

Lanthanide ion (Ln) chelating amphiphiles are powerful molecules for tailoring the magnetic response of polymolecular assemblies. Mixtures of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dimyristoyl-sn-glycero-3-phospho-ethanolamine-diethylene triaminepentaacetate (DMPE-DTPA) complexed to Ln deliver highly magnetically responsive bicelles. Their magnetic properties are readily tuned by changing the bicellar size or the magnetic susceptibility Δχ of the bilayer lipids. The former technique is intrinsically bound to the region of the phase diagram guarantying the formation of bicelles. Methods aiming towards manipulating the Δχ of the bilayer are comparatively more robust, flexible and lacking. Herein, we synthesized a new Ln chelating phospholipid using glutamic acid as a backbone: DMPE-Glu-DTPA. The chelate polyhedron was specifically engineered to alter the Δχ, whilst remaining geometrically similar to DMPE-DTPA. Planar asymmetric assemblies hundreds of nanometers in size were achieved presenting unprecedented magnetic alignments. The DMPE-Glu-DTPA/Ln complex switched the Δχ, achieving perpendicular alignment of assemblies containing Dy and parallel alignment of those containing Tm. Moreover, samples with chelated Yb were more alignable than the Tm chelating counterparts. Such a possibility has never been demonstrated for planar Ln chelating polymolecular assemblies. The physico-chemical properties of these novel assemblies were further studied by monitoring the alignment behavior at different temperatures and by including 16 mol% of cholesterol (Chol-OH) in the phospholipid bilayer. The DMPE-Glu-DTPA/Ln complex and the resulting assemblies are promising candidates for applications in numerous fields including pharmaceutical technologies, structural characterization of membrane biomolecules by NMR spectroscopy, as contrasting agents for magnetic resonance imaging, and for the development of smart optical gels.

Hydrogels delivering on-demand tailorable optical properties are formidable smart materials with promising perspectives in numerous fields, including the development of modern sensors and switches, the essential quality criterion being a defined and readily measured response to environmental changes. Lanthanide ion (Ln)-chelating bicelles are interesting building blocks for such materials because of their magnetic responsive nature. Imbedding these phospholipid-based nanodiscs in a magnetically aligned state in gelatin permits an orientation-dependent retardation of polarized light. The resulting tailorable anisotropy gives the gel a well-defined optical signature observed as a birefringence signal. These phenomena were only reported for a single bicelle-gelatin pair and required high magnetic field strengths of 8 T. Herein, we demonstrate the versatility and enhance the viability of this technology with a new generation of aminocholesterol (Chol-NH)-doped bicelles imbedded in two different types of gelatin. The highly magnetically responsive nature of the bicelles allowed to gel the anisotropy at commercially viable magnetic field strengths between 1 and 3 T. Thermoreversible gels with a unique optical signature were generated by exposing the system to various temperature conditions and external magnetic field strengths. The resulting optical properties were a signature of the gel's environmental history, effectively acting as a sensor. Solutions containing the bicelles simultaneously aligning parallel and perpendicular to the magnetic field directions were obtained by mixing samples chelating Tm and Dy. These systems were successfully gelled, providing a material with two distinct temperature-dependent optical characteristics. The high degree of tunability in the magnetic response of the bicelles enables encryption of the gel's optical properties. The proposed gels are viable candidates for temperature tracking of sensitive goods and provide numerous perspectives for future development of tomorrow's smart materials and technologies.