Nanoparticle-mediated IgE-receptor aggregation and signaling in RBL mast cells.

Journal of the American Chemical Society
Yu-Fen HuangWeihong Tan

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 (IgE-Fc epsilonRI) 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 ...Continue Reading

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