Amyloid-β (Aβ) peptides spontaneously aggregate into βand cross-β-sheets in model brain membranes. These nanometer sized can fuse into larger micrometer sized clusters and become extracellular and serve as nuclei for further plaque and fibril growth. Curcumin and homotaurine represent two different types of Aβ aggregation inhibitors. While homotaurine is a peptic antiaggregant that binds to amyloid peptides, curcumin is a nonpeptic molecule that can inhibit aggregation by changing membrane properties. By using optical and fluorescent microscopy, X-ray diffraction, and UV−vis spectroscopy, we study the effect of curcumin and homotaurine on Aβ 25−35 aggregates in synthetic brain membranes. Both molecules partition spontaneously and uniformly in membranes and do not lead to observable membrane defects or disruption in our experiments. Both curcumin and homotaurine were found to significantly reduce the number of small, nanoscopic Aβ aggregates and the corresponding βand cross-β-sheet signals. While a number of research projects focus on potential drug candidates that target Aβ peptides directly, membrane-lipid therapy explores membrane-mediated pathways to suppress peptide aggregation. Based on the results obtained, we conclude that membrane active drugs can be as efficient as peptide targeting drugs in inhibiting amyloid aggregation in vitro.

We used all-atom Molecular Dynamics (MD) computer simulations to study the formation of pre-polymers between the four nucleotides in RNA (AMP, UMP, CMP, GMP) in the presence of different substrates that could have been present in a prebiotic environment. Pre-polymers are C3′–C5′ hydrogen-bonded nucleotides that have been suggested to be the precursors of phosphodiester-bonded RNA polymers. We simulated wet–dry cycles by successively removing water molecules from the simulations, from ~60 to 3 water molecules per nucleotide. The nine substrates in this study include three clay minerals, one mica, one phosphate mineral, one silica, and two metal oxides. The substrates differ in their surface charge and ability to form hydrogen bonds with the nucleotides. From the MD simulations, we quantify the interactions between different nucleotides, and between nucleotides and substrates. For comparison, we included graphite as an inert substrate, which is not charged and cannot form hydrogen bonds. We also simulated the dehydration of a nucleotide-only system, which mimics the drying of small droplets. The number of hydrogen bonds between nucleotides and nucleotides and substrates was found to increase significantly when water molecules were removed from the systems. The largest number of C3′–C5′ hydrogen bonds between nucleotides occurred in the graphite and nucleotide-only systems. While the surface of the substrates led to an organization and periodic arrangement of the nucleotides, none of the substrates was found to be a catalyst for pre-polymer formation, neither at full hydration, nor when dehydrated. While confinement and dehydration seem to be the main drivers for hydrogen bond formation, substrate interactions reduced the interactions between nucleotides in all cases. Our findings suggest that small supersaturated water droplets that could have been produced by geysers or springs on the primitive Earth may play an important role in non-enzymatic RNA polymerization.