Pleiotropic Nanostructures Built from l-Histidine Show Biologically Relevant Multicatalytic Activities.

The essential amino acid histidine plays a central role in the manifestation of several metabolic processes, including protein synthesis, enzyme-catalysis, and key biomolecular interactions. However, excess accumulation of histidine causes histidinemia, which shows brain-related medical complications, and the molecular mechanism of such histidine-linked complications is largely unknown. Here, we show that histidine undergoes a self-assembly process, leading to the formation of amyloid-like cytotoxic and catalytically active nanofibers. The kinetics of histidine self-assembly was favored in the presence of Mg(II) and Co(II) ions. Molecular dynamics data showed that preferential noncovalent interactions dominated by H-bonds between histidine molecules facilitate the formation of histidine nanofibers. The histidine nanofibers induced amyloid cross-seeding reactions in several proteins and peptides including pathogenic Aß1-42 and brain extract components. Further, the histidine nanofibers exhibited oxidase activity and enhanced the oxidation of neurotransmitters. Cell-based studies confirmed the cellular internalization of histidine nanofibers in SH-SY5Y cells and subsequent cytotoxic effects through necrosis and apoptosis-mediated cell death. Since several complications including behavioral abnormality, developmental delay, and neurological disabilities are directly linked to abnormal accumulation of histidine, our findings provide a foundational understanding of the mechanism of histidine-related complications. Further, the ability of histidine nanofibers to catalyze amyloid seeding and oxidation reactions is equally important for both biological and materials science research.

Oil Red O based method for exosome labelling and detection.

With the realization of the role of exosomes in diseases, especially cancer, exosome research is gaining popularity in biomedical sciences. To understand exosome biology, their labelling and tracking studies are important. New and improved methods of exosome labelling for detection and tracking of exosomes need to be developed to harness their therapeutic and diagnostic potential. In this paper, we report a novel, simple and effective method of labelling and detecting exosomes using Oil Red O (ORO), a dye commonly used for lipid staining. Using ORO is a cost effective and easy approach with an intense red coloration of exosomes. Further, the issues faced with commonly used lipophilic dyes for exosome labelling like long-term persistence of dyes, aggregation and micelle formation of dyes, difficulty in distinguishing dye particles from labelled exosomes, and detection of large aggregates of dye or dye-exosome, are also resolved with ORO dye. This method shows good labelling efficacy with very sensitive detection and real-time tracking of the cellular uptake of exosomes.