Influence of macroscopic and microscopic interactions on kinetic rate constants: I. Role of the extended DLVO theory in determining the kinetic adsorption constant of proteins in aqueous media, using von Smoluchowski’s approach

In the case of adsorption in an aqueous medium of a hydrophilic protein (e.g. human serum albumin (HSA)) onto a hydrophilic solid substratum such as a clean glass surface, one has to deal with a macroscopic-level repulsion between HSA and glass at (generally) the majority of orientations of the protein molecules, and also a microscopic-level attraction between HSA and glass at (generally) the minority of orientations of the protein molecules. The first phenomenon represents von Smoluchowski’s improbability of adhesion or adsorption and the second represents the probability of adhesion or adsorption [1]. Both contingencies have to be taken into account in determining von Smoluchowski’s net probability factor, f of the kinetic association constant, k_a, pertaining to protein adsorption. In the exceptional case where both the protein and the solid substratum are hydrophobically/hydrophilically and electrostatically neutral, f=1, and the k_a-value is only proportional to the diffusion coefficient of the protein [2]. In order to determine the contributions of both the macroscopic repulsion and the microscopic attraction pertaining to the kinetics of protein adsorption, an extended DLVO analysis (XDLVO) needs to be done on these interactions at all distances and at all protein orientations. The XDLVO analysis comprises the Lewis acid–base interaction energies as a function of distance, in addition to the Lifshitz–van der Waals and the electrokinetic interaction energies [2, 3, 4 and 5].