Fig. 6. Schematic illustration of time- and surface property-based evolution of protein corona.

Protein corona formation and evolution is a spatiotemporal process, in which the outer and inner layers organize the structure of protein corona companying with dynamic exchange of coronal composition and protein abundance with time, surface properties, source, etc. The interaction between nanoparticles and proteins and between NP-proteins and proteins drives the formation of hard and soft coronas, for which both interaction systems exhibit distinct binding affinity. The formation of the soft and hard corona is a time- and surface coating-dependent thermodynamic and kinetics process, in which the components and the number of protein species of both corona change with time, and the surface properties of nanoparticles such as surface chirality are also a dominant factor for the evolution process. In addition, the source of biological fluids, protein abundance, and other factors are involved in corona formation and evolution. The spherical structures with gray blue refer to Cu₂S NPs; while the structures with purple, green, and light blue, represent various proteins with high, medium, and low binding affinity to NPs.