Rapid Analysis of Weak Protein Interactions Using Self-Interaction Nanoparticle Spectroscopy

Weak protein interactions regulate diverse protein condensation behavior (e.g., crystallization and aggregation), yet 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 high-throughput manner (Tessier et al., J Am Chem Soc, 2008). In this presentation we will discuss different approaches of 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 our use of SINS for rapidly analyzing the self-association behavior of a library of homologous antibody fragments with the goal of improving the design and selection of aggregation-resistant antibodies.