Human serum albumin interactions with C₆₀ fullerene studied by spectroscopy, small-angle neutron scattering, and molecular dynamics simulations

Concern about the toxicity of engineered nanoparticles, such as the prototypical nanomaterial C₆₀ fullerene, continues to grow. While, evidence continues to mount that C₆₀ and its derivatives may pose health hazards, the specific molecular interactions of these particles with biological macromolecules require further investigation. In this article, we report combined experimental and theoretical studies on the interaction of one of the most prevalent proteins in the human body, human serum albumin (HSA), with C₆₀ in an aqueous environment. The C₆₀-HSA interaction was probed by circular dichroism (CD) spectroscopy, small-angle neutron scattering (SANS), and atomistic molecular dynamics (MD) simulations to understand C₆₀-driven changes in the structure of HSA in solution. The CD spectroscopy demonstrates that the secondary structure of the protein decreases in α-helical content in response to the presence of C ₆₀ (0.68 nm in diameter). Similarly, C₆₀ produces subtle changes in the solution conformation of HSA (an 8.0 nm × 3.8 nm protein), as evidenced by the SANS data and MD simulations, but the data do not indicate that C₆₀ changes the oligomerization state of the protein, such as by inducing aggregation. The results demonstrate that the interaction is not highly disruptive to the protein in a manner that would prevent it from performing its physiological function.