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 β-lactoglobulin (BLG)
in a dose-dependent manner. Helix loss is corelated with the near
stoichiometric formation of β-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.