Impact of intermolecular attraction and repulsion on molecular diffusion and virial coefficients of spheroidal and rod-shaped proteins

Abstract

Recognition of protein intermolecular interactions is a key factor for the study and manipulation of protein activity in living systems and biotechnology formulations. Experimental parameter that is sensitive to intermolecular interactions is molecular diffusion. This work presents an extension of an earlier work where we proposed the complementary use of pulsed field gradient nuclear magnetic resonance (PFG NMR) and dynamic light scattering (DLS) to study the specific features of intermolecular interactions via protein translational diffusion. PFG NMR methodology characterizes the thermal motion of protein by means of the self-diffusion coefficient and friction formalism. DLS experiments provide the protein collective (or mutual) diffusion coefficient, which evaluates the direct, non-specific intermolecular interactions of proteins by means of virial coefficients. Theoretical analysis of obtained experimental diffusion data is based on the combination of the friction formalism of nonequilibrium thermodynamics (Vink approach) with the Deryaguin-Landau-Verwey-Overbeek (DLVO) theory. To evaluate the electrostatic potential of proteins with different shape - spheroidal alfa-chymotrypsin (ChTr) and the rod-shaped fibrinogen (Fg) we applied the model of “porous” colloid particles. Our analysis has shown that the atypical local decrease of collective diffusion relative to self-diffusion is a consequence of the dominance of van der Waals attraction over electrostatic repulsion for the rod-shaped Fg.