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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.

Amphiphilic compounds, such as phospholipids or surface-active substances, are present in biological systems and can be part of pharmaceutical formulations. As a consequence, all pharmaceutically active ingredients will encounter amphiphilic compounds, either in the formulation or after administration. With the growing interest in peptide-based pharmaceuticals, there is a need to enhance the understanding of the interactions between peptides and amphiphilic compounds.

In this particular study, we have chosen to study mixtures of the comparatively small cyclical octapeptide lanreotide and the conventional anionic surfactant sodium dodecylsulfate (SDS). This was done by examining the self-assembly structures formed in lanreotide-SDS mixtures using light scattering and small-angle X-ray scattering (SAXS).

Above the critical micelle concentration (cmc) of SDS, the large excess of SDS could solubilize all lanreotide and form small micelles with lanreotide attached to the interface. Upon dilution to concentrations below the cmc of SDS, a suspension with dispersed solid nanoparticles is formed. The solid nanoparticles grow in size with decreasing concentration and, eventually, precipitate. The precipitated material is arranged in a liquid crystalline micellar phase, consisting of small close-packed SDS micelles with peptide adsorbed at the interface.

We were able to conclude that lanreotide does not form mixed micelles with SDS, indicating that it lacks the amphiphilic properties required to integrate fully with SDS behaving as a cosurfactant. In contrast, lanreotide attaches to the interface of SDS micelles, resembling the interactions of polymers, proteins, and nucleic acids with surfactants.