NSF Award
2203740
With support from the Macromolecular, Supramolecular and Nanochemistry Program in the Division of Chemistry, Professor Jeremy Driskell of Illinois State University is combining chemical synthesis and advanced chemical analysis tools to study how proteins adsorb onto gold nanoparticles and maintain or enhance their biological function. The study identifies key interactions between the protein and nanoparticle that can be exploited to prevent protein unfolding and to facilitate controlled release from the nanoparticle surface. Professor Driskell and his students are chemically modifying proteins to install chemical anchors with high affinity for the gold nanoparticles and measuring the stability and biological function of the adsorbed protein layer. Their discoveries could lead to predictive design parameters to form robust and highly functional protein-nanoparticle probes and broadly impact modern biosensing, medical imaging, drug delivery, and biocatalysis. This project provides support for undergraduate students to participate in an immersive research experience to learn advanced analytical techniques and gain an appreciation for a multidisciplinary approach to problem solving. Additionally, in collaboration with the Illinois Research Academy, Dr. Driskell and his supported undergraduate students provide high school students with an intense, yet supervised, research experience. <br/><br/>A detailed understanding of the protein-nanoparticle interface is critical to mitigate structural changes that negatively impact the function of the adsorbed protein and to leverage stabilizing interactions that enhance protein function. Surface accessible thiols on a protein are hypothesized to be primarily responsible for the adsorption onto gold nanoparticles and the formation of a hard corona; thus, the ability to precisely control the number of protein thiols can be exploited to optimize bioconjugate function. A synthetic strategy is proposed to install thiol functional groups on a series of enzymes. The reaction conditions are optimized to precisely control the number of thiols, and monitored by high-resolution mass spectrometry, zeta potential, and Ellman’s reagent. Adsorption affinity, quantitatively assessed using nanoparticle tracking analysis, and protein exchange rate, measured via a competitive protein binding, is correlated with the number of surface accessible thiols presented by the protein. Additionally, the structure and function of the free and nanoparticle-immobilized protein is compared to identify any relationship between protein thiolation and protein structure/function upon adsorption to a nanoparticle. Successful completion of this project drives the novel design of highly active and stable protein-AuNP conjugates that is critically needed to advance bioconjugate-enabled platform technologies.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
