Competitive adsorption of multiple proteins to nanoparticles: the Vroman effect revisited

Proteins adsorbed from the blood plasma change nanoparticles inter- actions with the surrounding biological environment. In general, the ad- sorption of multiple proteins has a non-monotonic time dependence, that is, proteins adsorbed at first may slowly be replaced by others. This “Vro- man effect” leads to a highly dynamic protein corona on nanoparticles that profoundly influences the immune response of the body. Thus, the temporal evolution of the corona must be taken into account when consid- ering applications of nanocarriers in, e.g., nanomedicine or drug delivery. Up to now, the Vroman effect is explained solely in terms of diffusion: Smaller proteins which diffuse faster are adsorbed first while larger ones, having a stronger interaction with the surface, are preferred at equilib- rium. Here we use dynamic density functional theory (DDFT) including steric and electrostatic interactions to provide a full model for the tem- poral evolution of the protein corona. In particular, we demonstrate that proper consideration of all interactions leads to Vroman-like adsorption signatures in widely different scenarios. Moreover, consideration of ener- getic terms predicts both competitive as well as co-operative adsorption. In this way, DDFT provides a reacher picture of the evolution of the dynamic protein corona