Serum Albumin Aggregation Facilitated by Cobalt and Chromium Metal Ions.

Abstract

The interaction of serum proteins with cobalt (Co) and chromium (Cr) ions is poorly understood, but it is suspected to result in protein aggregation, which may alter the corrosion process of biomedical CoCr alloys or result in adverse health effects. Here, we study the aggregation ability and mechanism of bovine serum albumin (BSA) induced or accelerated by aqueous Co(II) and Cr(III) ions. The metal salts were selected by chemical speciation modeling, and they did not affect the pH or precipitate under simulated physiological conditions (150 mM NaCl and pH 7.3). The counterion of Cr(III) influenced the binding to BSA only at physiologically irrelevant low ionic strength. This study used a variety of spectroscopic and light scattering methods. It was determined that both metal ions and an equimolar mixture of metal ions have the potential to induce protein aggregation. Melting curves collected by circular dichroism spectroscopy indicate that Co(II) significantly reduced BSA's melting temperature when compared with Cr(III) or an equimolar mixture of Co(II) and Cr(III), both of which increased the melting temperature of BSA. The metal ions in solution preferentially interacted with BSA, resulting in the depletion of metal ions from the surrounding protein-free solution. Finally, this study suggests that the likely mechanism for Co(II)- and Cr(III)-induced BSA aggregation is salt bridging between protein molecules.