The diffusion interaction parameter kD is a helpful parameter to assess weak inter-particle interactions and is generally employed to understand and predict colloidal protein stability. It is, for example, applied in formulation screening to identify promising buffer conditions early in the development pipeline. Note that kD is unrelated to the dissociation constant Kd which is a parameter to describe binding affinities.

Non-specific protein-protein interactions primarily originate from charged or hydrophobic residues being in close proximity and are therefore concentration-dependent. Such interactions will change the diffusion behavior of the solvated particles and are reflected in the observed diffusion coefficient D. K_D is a measure to describe this concentration-dependence of D as a result of inter-particle interaction and is calculated by fitting the D(c) curve with a straight line:

where D is the translational diffusion coefficient, D₀ the diffusion coefficient at infinite dilution, k_D the first order diffusion interaction parameter, and c the particle concentration.

Positive kD values indicate repulsive forces, because particles repelling each other will diffuse faster with increasing concentration. Negative values reflect attraction, because particles attracting each other will diffuse slower with increasing concentration. Since attractive interactions between proteins have been correlated with higher aggregation propensity, negative kD are typically associated with lower colloidal stability and are avoided in biotherapeutics development. kD is used in this manner to rank buffer conditions.