Identification of Receptor Binding to the Biomolecular Corona of Nanoparticles

TLDR

Biomolecules adsorbed on nanoparticles confer a biological identity that mediates interactions with cells and barriers, yet the manner in which they are presented on the particle surface in biological milieu remains unclear. The study aims to identify key protein recognition motifs in the nanoparticle corona and link them to specific cell‑receptor interactions. Using an immuno‑mapping technique to quantify epitope presentations of LDL and IgG in the serum corona, combined with a receptor expression system, the authors demonstrate that both proteins display functional motifs recognized by LDLR and FcγRI. The results indicate that biomolecular adsorption labels nanoparticles for multiple pathways, enabling them to be mistaken for endogenous lipoproteins or exogenous viral particles.

Abstract

Biomolecules adsorbed on nanoparticles are known to confer a biological identity to nanoparticles, mediating the interactions with cells and biological barriers. However, how these molecules are presented on the particle surface in biological milieu remains unclear. The central aim of this study is to identify key protein recognition motifs and link them to specific cell-receptor interactions. Here, we employed an immuno-mapping technique to quantify epitope presentations of two major proteins in the serum corona, low-density lipoprotein and immunoglobulin G. Combining with a purpose-built receptor expression system, we show that both proteins present functional motifs to allow simultaneous recognition by low-density lipoprotein receptor and Fc-gamma receptor I of the corona. Our results suggest that the "labeling" of nanoparticles by biomolecular adsorption processes allows for multiple pathways in biological processes in which they may be "mistaken" for endogenous objects, such as lipoproteins, and exogenous ones, such as viral infections.