Dissecting the interaction between Graphene Oxide and Human Transferrin via biophysical, biochemical and in-silico approaches: Implications for nanomaterial anti-fibrillation properties and protein structure

Abstract

Human Transferrin (HTF) plays a pivotal role in numerous neurological therapies by carrying drugs and nanomaterials through the challenging blood-brain barrier. Nonetheless, the binding of HTF with highly relevant nanomaterials is not fully comprehended. Here, the nanomaterial graphene oxide (GO) has been obtained and their interaction with HTF in the native and fibrillar form has been investigated, by employing multi-spectroscopic, modeling, and microscopic techniques. The fluorescence results reveal that GO quenches the HTF intrinsic fluorescence by following a mix of static and dynamic mechanisms, and the GO-HTF complex formation has been confirmed by UV-Vis spectroscopy. Additionally, HTF attaches firmly to GO (KS≈ 106M−1) through mainly by hydrophobic and hydrogen bonds (according to determined ΔH=-23.77±1.03 kJ.mol−1 and ΔS= +39.53 ± 1.69 J.mol−1.K−1). Further, the in-silico investigation has evidenced the residues and chemical groups involved in HTF-GO interaction. Furthermore, SEM images reveal the formation and inhibition of HTF aggregates by GO, and spectroscopic methods reveal the related protein structural modification involved in the fibrillation process. In summary, all the results open questions concerning GO use for many neurological therapies.