Peptide based nano-assemblies with their self-organizing ability has shown lot of promise due to their high degree of thermal and chemical stability, for biomaterial fabrication. Developing an effective way to control the organization of these structures is important for fabricating application-oriented materials at the molecular level. The present study reports the impact of electric and magnetic field-mediated perturbation of the self-assembly phenomenon, upon the chemical and structural properties of diphenylalanine assembly. Our studies show that, electric field effectively arrests aggregation and self-assembly formation, while the molecule is allowed to anneal in the presence of applied electric fields of varying magnitudes, both AC and DC. The electric field exposure also modulated the morphology of the self-assembled structures without affecting the overall chemical constitution of the material. Our results on the modulatory effect of the electric field are in good agreement with theoretical studies based on molecular dynamics reported earlier on amyloid forming molecular systems. Furthermore, we demonstrate that the self-assemblies formed post electric-field exposure, showed difference in their crystal habit. Modulation of nano-level architecture of peptide based model systems with external stimulus, points to a potentially rewarding strategy to re-work proven nano-materials to expand their application spectrum.

The aggregation of β-amyloid peptides is a key event in the formative stages of Alzheimer’s disease. Promoting folding and inhibiting aggregation was reported as an effective strategy in reducing Aβ-elicited toxicity. This study experimentally investigates the influence of the external electric field (EF) and magnetic field (MF) of varying strengths on the in vitro fibrillogenesis of hydrophobic core sequence, Aβ16–22, and its parent peptide, Aβ1–42. Biophysical methods such as ThT fluorescence, static light scattering, circular dichroism, and infrared spectroscopy suggest that EF has a stabilizing effect on the secondary structure, initiating a conformational switch of Aβ16–22 and Aβ1–42 from β to non-β conformation. This observation was further corroborated by dynamic light scattering and transmission electron microscopic studies. To mimic in vivo conditions, we repeated ThT fluorescence assay with Aβ1–42 in human cerebrospinal fluid to verify EF-mediated modulation. The self-seeding of Aβ1–42 and cross-seeding with Aβ1–40 to verify that the autocatalytic amplification of self-assembly as a result of secondary nucleation also yields comparable results in EF-exposed and unexposed samples. Aβ-elicited toxicity of EF-treated samples in two neuroblastoma cell lines (SH-SY5Y and IMR-32) and human embryonic kidney cell line (HEK293) were found to be 15–38% less toxic than the EF untreated ones under identical conditions. Experiments with fluorescent labeled Aβ1–42 to correlate reduced cytotoxicity and cell internalization suggest a comparatively smaller uptake of the EF-treated peptides. Our results provide a scientific roadmap for future noninvasive, therapeutic solutions for the treatment of Alzheimer’s disease.

No abstract

The ability to modulate self-assembly is the key to manufacture application-oriented materials. In this study, we investigated the effect of three independent variables that can modulate the catalytic activity of...

We employed a reductionist approach in designing the first heterochiral tripeptide that forms a robust heterogeneous short peptide catalyst similar to the “histidine brace” active site of lytic polysaccharide monooxygenases. The histidine brace is a conserved divalent copper ion-binding motif that comprises two histidine side chains and an amino group to create the T-shaped 3N geometry at the reaction center. The geometry parameters, including a large twist angle (73°) between the two imidazole rings of the model complex, are identical to those of native lytic polysaccharide monooxygenases (72.61°). The complex was synthesized and characterized as a structural and functional mimic of the histidine brace. UV–vis, vis-circular dichroism, Raman, and electron paramagnetic resonance spectroscopic analyses suggest a distorted square-pyramidal geometry with a 3N coordination at pH 7. Solution- and solid-state NMR results further confirm the 3N coordination in the copper center of the complex. The complex is pH-dependent and could catalyze the oxidation of benzyl alcohol in water to benzaldehyde with yields up to 82% in 3 h at pH 7 and above at 40 °C. The catalyst achieved 100% selectivity for benzaldehyde compared to conventional copper catalysis. The design of such a minimalist building block for functional soft materials with a pH switch can be a stepping stone in addressing needs for a cleaner and sustainable future catalyst.