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 Mg 2+ and Cu 2+ 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 Mg 2+ and Cu 2+ ions.