Nanoparticle-Mediated IgE−Receptor Aggregation and Signaling in RBL Mast Cells

Abstract

Complex cell behaviors are usually triggered by multivalent ligands that first bind to membrane receptors and then promote receptor clustering, thus altering intracellular signal transduction. While it is possible to produce such altered signal transduction by synthetic means, the development of chemically defined multivalent ligands of effectors is sometimes difficult and tedious. Specifically, the average spacing between two binding sites within an antibody and the average distance between receptors on the cell membrane are usually larger than most organic molecules. In this study, we directly address these challenges by demonstrating how gold nanoparticles (AuNPs) of precisely controlled mean diameters can be easily synthesized and surface-modified with dinitrophenyl (DNP) at an equally well-controlled ligand density, or spacing. We found that both nanoparticle size and surface ligand density play key regulatory roles in the process of membrane antibody-receptor (IgEFcεRI) binding and cross-linking, which, in turn, leads to degranulation and consequent release of chemical mediators on rat basophilic leukemia cells. In addition, by adjusting DNP-AuNP architecture we discovered that our conjugates could either promote or inhibit cellular activation.Thus, these results demonstrate that nanoparticles not only serve as simple platforms for multivalent binding, but also as mediators for key biological functions. As such, the findings we report here may provide insight into the use of nanoparticles as a comprehensive tool for use in detailed receptor/ ligand interaction studies and in the design of nanoscale delivery and therapeutic systems.

Particle shape enhances specificity of antibody-displaying nanoparticles

“…Such effects previously were reported based on experiments and theory (35,36). Multivalent gold nanoparticles coated with dinitrophenyl have shown a similar bell-shaped dose-response curve due to cross-linking of IgEFceRI receptor complexes in RBL-2H3 mast cells (37). Although the studies presented here suggest that enhanced uptake of nanorods can be explained by enhanced surface binding, additional factors associated with multivalent interactions and penetration through the glycocalyx also are likely explanations for the experimental observations (SI Text, section 5).…”

Polymer‐Coated Metal‐Oxide Nanoparticles Inhibit IgE Receptor Binding, Cellular Signaling, and Degranulation in a Mast Cell‐like Cell Line

“…These findings confirm the results of Huang et. al.,20 in demonstrating that NPs can interact directly with FcεRI and also extend these results by reporting that even smaller particles (3–10 nm) can inhibit cell effector functions.…”

“…Huang et al20 showed that DNP‐albumin labeled gold NPs directly stimulated FcεRI‐mediated responses by providing cross‐linking of receptors. However, bare gold particles themselves did not bind to FcεRI, nor did they alter degranulatory behavior.…”

Aptamer biosensor for dopamine based on a gold electrode modified with carbon nanoparticles and thionine labeled gold nanoparticles as probe

“…AuNPs has been used as substrate to immobilize electrochemical marker to amplify the electrochemical signal in recent years. It's obviously that there needs no enzymes in this procedure [24].…”