Cardiolipin (CL) plays an important role in administering the structural organization of biological membranes and therefore helps maintaining the integer membrane functionality. CL has a dimeric structure consisting of four acyl chains and two phosphate groups. With its unusual structure, the phospholipid is responsible for curvature formation in CL containing biological membranes. The acidic properties of the phosphate head groups are still not sufficiently investigated since there are controversial results in literature. The main aim of this work was to gain deeper insights into the influence of the pH on the ionization degree of CL. During the experiments, it became clear that the used ultrapure water contained traces of calcium. These unexpected calcium ions had a major impact on the behavior of CL monolayers. Therefore, the focus was put on the analysis of CL layers without and with EDTA in the subphase used to complex divalent calcium ions. For the analyses, traditional surface pressure (π) – molecular area (A) isotherm experiments combined with total reflection x‐ray fluorescence (TRXF) and grazing incidence x‐ray diffraction (GIXD) have been used.

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.

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Multivalent display of identical ultrashort (only 2-3 amino acids long) antimicrobial peptides (AMPs) was used in order to create potential new antimicrobial agents. A series of small synthetic arginine and tryptophan containing peptides was synthesized and covalently bound to two different trivalent scaffold molecules using the copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. The effect of steric preorganization of AMPs on the antibacterial activity was studied using a 1,3,5-tris(azidomethyl)-benzene and a 1,3,5-tris(azidomethyl)-2,4,6-triethylbenzene substituted scaffold. The comparison of these two scaffolds showed that preorganisation leads to at least twice as active compounds. We furthermore obtained a synergistic effect and could show that the presence of a certain number of amino acids in close proximity is more important than their relative spatial orientation.