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Aggregation of peptide molecules into amyloid fibrils is a characteristic feature of several degenerative diseases. However, the details behind amyloid-formation, and other self-assembled peptide aggregates, remain poorly understood. In this study, we have used small-angle X-ray scattering (SAXS), static and dynamic light scattering (SLS and DLS) as well as cryogenic transmission electron microscopy (cryo-TEM) to determine the structural geometry of self-assembled peptide aggregates in various dilute aqueous solutions. Pramlintide was used as a model peptide to assess the aggregation behaviour of an amyloid-forming peptide. The effects of adding sodium chloride (NaCl), sodium thiocyanate (NaSCN), and sodium fluoride (NaF) and the co-solvent dimethyl sulfoxide (DMSO) on the aggregation behaviour were studied. Our scattering data analysis demonstrates that small oligomeric fibrils aggregate to form networks of supramolecular assemblies with fractal dimensions. The choice of anion in small amounts of added salt has a significant impact on the size of the fibrils as well as on the fractal dimensions of supramolecular clusters. In DMSO the fractal dimension decreased with increasing DMSO concentration, indicating the formation of a less compact structure of the supramolecular assemblies. The peptide pramlintide forms oligomeric species in solution, which make up a supramolecular network characterised by fractal dimensions. The fractal dimension of the network depends on solvent additive.

We have observed ultrasmall unilamellar vesicles, withdiametersof less than 20 nm, in mixtures of the tricyclic antidepressant drugamitriptyline hydrochloride (AMT) and the unsaturated zwitterionicphospholipid 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) in physiologicalsaline solution. The size and shape of spontaneously formed self-assembledaggregates have been characterized using complementary techniques,i.e., small-angle neutron and X-ray scattering (SANS and SAXS) andcryo-transmission electron microscopy (cryo-TEM). We observe rodlikemixed micelles in more concentrated samples that grow considerablyin length upon dilution, and a transition from micelles to vesiclesis observed as the concentration approaches the critical micelle concentrationof AMT. Unlike the micelles, the spontaneously formed vesicles decreasein size with each step of dilution, and ultrasmall unilamellar vesicles,with diameters as small as about 15 nm, were observed at the lowestconcentrations. The spontaneously formed ultrasmall unilamellar vesiclesmaintain their size for as long we have investigated them (i.e., severalmonths). To the best of our knowledge, such small vesicles have neverbefore been reported to form spontaneously in a biocompatible phospholipid-basedsystem. Most interestingly, the size of the vesicles was observedto be strongly dependent on the chemical structure of the phospholipid,and in mixtures of AMT and the phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine(DMPC), the vesicles were observed to be considerably larger in size.The self-assembly behavior in the phospholipid-drug surfactantsystem in many ways resembles the formation of equilibrium micellesand vesicles in mixed anionic/cationic surfactant systems.

The influence and interaction of the ionizable amphiphilic drug amitriptyline hydrochloride (AMT) on a 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) phospholipid bilayer supported on a silica surface have been investigated using a combination of neutron reflectometry and quartz crystal microbalance with dissipation monitoring. Adding AMT solutions with concentrations 3, 12, and 50 mM leaves the lipid bilayer mainly intact and we observe most of the AMT molecules attached to the head-group region of the outer bilayer leaflet. Virtually no AMT penetrates into the hydrophilic head-group region of the inner leaflet close to the silica surface. By adding 200 mM AMT solution, the lipid bilayer dissolved entirely, indicating a threshold concentration for the solubilization of the bilayer by AMT. The observed threshold concentration is consistent with the observation that various bilayer structures abruptly transform into mixed AMT-DOPC micelles beyond a certain AMT-DOPC composition. Based on our experimental observations, we suggest that the penetration of drug into the phospholipid bilayer, and subsequent solubilization of the membrane, follows a two-step mechanism with the outer leaflet being removed prior to the inner leaflet.

Interest in creating magnetic metamaterials has led to methods for growing superstructures of magnetic nanoparticles. Mesoscopic crystals of maghemite (gamma-Fe2O3) nanoparticles can be arranged into highly ordered body-centered tetragonal lattices of up to a few micrometers. Although measurements on disordered ensembles have been carried out, determining the magnetic properties of individual mesoscopic crystals is challenging due to their small total magnetic moment. Here, we overcome these challenges by utilizing sensitive dynamic cantilever magnetometry to study individual micrometer-sized gamma-Fe2O3 mesocrystals. These measurements reveal an unambiguous cubic anisotropy, resulting from the crystalline anisotropy of the constituent maghemite nanoparticles and their alignment within the mesoscopic lattice. The signatures of anisotropy and its origins come to light because we combine the self-assembly of highly ordered mesocrystals with the ability to resolve their individual magnetism. This combination is promising for future studies of the magnetic anisotropy of other nanoparticles, which are too small to investigate individually.