Self-Interaction Nanoparticle Spectroscopy: A Nanoparticle-Based Protein Interaction Assay

Weak protein interactions have broad relevance to the fields of biology and biotechnology. For example, these interactions govern the assembly of proteins into crystals for structural analysis, as well as both the aggregation of therapeutic proteins in vitro and disease-related proteins in vivo. Despite the importance of these interactions, they are notoriously difficult to characterize, especially in a high-throughput manner. We are developing a nanoparticle-based platform, namely self-interaction nanoparticle spectroscopy (SINS), to detect protein self-interactions in a parallel manner (Tessier et al., J Am Chem Soc, 2008). In this presentation we will discuss different approaches to modifying gold nanoparticles for efficient, stable immobilization of proteins with diverse physical properties. Moreover, we will demonstrate that protein self-interactions can be characterized using SINS in good agreement with measurements of osmotic second virial coefficients. Finally, we will discuss future directions for integrating SINS into the design and selection of aggregation-resistant protein therapeutics.