Interfacial Interactions between Nanoplastics and Biological Systems: toward an Atomic and Molecular Understanding of Plastics-Driven Biological Dyshomeostasis.

Micro- and nano-plastics (NPs) are found in human milk, blood, tissues, and organs and associate with aberrant health outcomes including inflammation, genotoxicity, developmental disorders, onset of chronic diseases, and autoimmune disorders. Yet, interfacial interactions between plastics and biomolecular systems remain underexplored. Here, we have examined experimentally, in vitro, in vivo, and by computation, the impact of polystyrene (PS) NPs on a host of biomolecular systems and assemblies. Our results reveal that PS NPs essentially abolished the helix-content of the milk protein ß-lactoglobulin (BLG) in a dose-dependent manner. Helix loss is corelated with the near stoichiometric formation of ß-sheet elements in the protein. Structural alterations in BLG are also likely responsible for the nanoparticle-dependent attrition in binding affinity and weaker on-rate constant of retinol, its physiological ligand (compromising its nutritional role). PS NP-driven helix-to-sheet conversion was also observed in the amyloid-forming trajectory of hen egg-white lysozyme (accelerated fibril formation and reduced helical content in fibrils). Caenorhabditis elegans exposed to PS NPs exhibited a decrease in the fluorescence of green fluorescent protein-tagged dopaminergic neurons and locomotory deficits (akin to the neurotoxin paraquat exposure). Finally, in silico analyses revealed that the most favorable PS/BLG docking score and binding energies corresponded to a pose near the hydrophobic ligand binding pocket (calyx) of the protein where the NP fragment was found to make nonpolar contacts with side-chain residues via the hydrophobic effect and van der Waals forces, compromising side chain/retinol contacts. Binding energetics indicate that PS/BLG interactions destabilize the binding of retinol to the protein and can potentially displace retinol from the calyx region of BLG, thereby impairing its biological function. Collectively, the experimental and high-resolution in silico data provide new insights into the mechanism(s) by which PS NPs corrupt the bimolecular structure and function, induce amyloidosis and onset neuronal injury, and drive aberrant physiological and behavioral outcomes.

Caffeic acid recarbonization: A green chemistry, sustainable carbon nano material platform to intervene in neurodegeneration induced by emerging contaminants.

Environmental agents such as pesticides, weedicides and herbicides (collectively referred to as pesticides) are associated with the onset and pathogenesis of neurodegenerative disorders such as Parkinson's (PD) and Alzheimer's (AD) diseases. The development of blood-brain barrier (BBB)-penetrating therapeutic candidates to both prevent and treat the aforementioned xenotoxicant-induced neurodegenerative disorders remains an unmet need. Here, we examine whether caffeic-acid based Carbon Quantum Dots (CACQDs) can intervene in pesticide-associated onset and progress of the PD phenotype. Pulse-chase fluorescence analyses revealed that CACQDs intervene in the soluble-to-toxic transformation of the amyloid-forming protein model Hen Egg White Lysozyme (HEWL). The sp2-rich CACQDs also scavenged free radicals, a milestone along the PD trajectory. In-vitro, CACQDs introduced into a human neuroblastoma-derived cell line (SH-SY5Y) demonstrated negligible cytotoxicity up to 5 mg/mL and protected the cell line against oxidative stress-induced neuronal injury induced by the pesticide and potent neurotoxin, paraquat. Our findings suggest that the potentially BBB-penetrating CACQDs derived from caffeic acid hold promise for mitigating neurodegenerative disorders associated with environmental pesticides and xenobiotic neurotoxicants. Importantly, CACQDs sourced from coffee, coupled with their facile synthesis, represent a sustainable, green chemistry platform for generating interventional candidates in neurodegeneration.