Mapping and identification of soft corona proteins at nanoparticles and their impact on cellular association

TLDR

Nanoparticle biological identity is largely inferred from the hard protein corona, while the composition and relevance of the soft corona remain unclear due to limited separation techniques. The study aims to identify weakly interacting corona proteins on silica and polystyrene nanoparticles. This was achieved by applying an in situ click‑chemistry reaction to capture these proteins. The captured proteins were also found in the hard corona but were enriched, indicating that hard versus soft corona differ mainly in binding strength; these weakly interacting proteins modulate nanoparticle–cell association through their dynamic behavior, underscoring the need to consider weak interactions at nano‑bio interfaces.

Abstract

The current understanding of the biological identity that nanoparticles may acquire in a given biological milieu is mostly inferred from the hard component of the protein corona (HC). The composition of soft corona (SC) proteins and their biological relevance have remained elusive due to the lack of analytical separation methods. Here, we identify a set of specific corona proteins with weak interactions at silica and polystyrene nanoparticles by using an in situ click-chemistry reaction. We show that these SC proteins are present also in the HC, but are specifically enriched after the capture, suggesting that the main distinction between HC and SC is the differential binding strength of the same proteins. Interestingly, the weakly interacting proteins are revealed as modulators of nanoparticle-cell association mainly through their dynamic nature. We therefore highlight that weak interactions of proteins at nanoparticles should be considered when evaluating nano-bio interfaces.