NMR and dynamic light scattering give different diffusion information for short-living protein oligomers. Human serum albumin in water solutions of metal ions

Diffusive behavior of human serum albumin (HSA) in the presence of Mg2+ and Cu2+ ions was studied by pulsed field gradient nuclear magnetic resonance (PFG NMR) and dynamic light scattering (DLS). According to NMR data yielding measurements of HSA self-diffusion coefficient, a weighted average of the protein monomers and oligomers diffusion mobility in the presence of metal ions was observed. While the short-time collective diffusion measured by DLS showed one type of diffusing species in ion-free HSA solution and two molecular forms of HSA in the presence of metal ions. The light intensity correlation function analysis showed that HSA oligomers have a limited lifetime (lower limit is about 0.4 ms) intermediate between characteristic time scales of PFG NMR and DLS experiments. For a theoretical description of concentration dependence of HSA self- and collective diffusion coefficients, the phenomenological approach based on the frictional formalism of non-equilibrium thermodynamics was used (Vink theory), allowing analysis of the solvent-solute and solute-solute interactions in protein solutions. In the presence of metal ions, a significant increase of HSA protein-protein friction coefficient was shown. Based on theoretical analysis of collective diffusion data, the positive values of second virial coefficients A(2) for HSA monomers were obtained. The A(2) values were found to be higher for the HSA with metal ions compared with the ion-free HSA solution. This is due to the more pronounced contribution of repulsion in protein-protein interactions of HSA monomers in the presence of Mg2+ and Cu2+ ions.

Automated summary

The diffusive behavior of human serum albumin (HSA) in the presence of Mg2+ and Cu2+ ions was studied using PFG NMR and DLS. The study found that the presence of metal ions affected the diffusion mobility of HSA monomers and oligomers, and the interaction between protein monomers was more pronounced in the presence of metal ions.