CAREER: Understanding Nanoparticle-induced Changes to Protein Structure

Vanderbilt University, Nashville TN

Investigators

Abstract

With support from the Chemical Structure, Dynamics, and Mechanisms A (CSDM-A) Program in the Division of Chemistry, Lauren Buchanan of Vanderbilt University is developing methods capable of measuring nanoparticle-induced changes to protein structure using advanced spectroscopic methods. Understanding these changes requires an experimental approach capable of observing nanoparticle-bound proteins with high structural resolution, a technological challenge due to sample heterogeneity and broad, overlapping spectral features. Dr. Buchanan and her students will combine two-dimensional infrared spectroscopy and isotopic labeling to provide insight into both the structure and dynamics of protein-nanomaterial interactions. Together, these techniques allow structural changes to be localized to individual residues within proteins. Discoveries made through this investigation are expected to improve understanding of the effects of nanoparticle exposure on biological systems and facilitate the design of bio-nano conjugated materials for applications in chemistry, biology, and materials science. Both graduate and undergraduate students actively participate in this biophysical chemistry research using advanced spectroscopic techniques. Dr. Buchanan also oversees “Young Scientist”, a research journal for high school students. Under this award, the role of nanoparticle composition, size, and composition on the secondary structure of peptides and proteins is being studied using two-dimensional infrared spectroscopy. To achieve this level of resolution, site-specific vibrational probes are also being employed. In so doing, spectral congestion will be reduced so that questions related to how inhibition or acceleration of peptide self-assembly by nanoparticles affects the structural organization and thermodynamic stability of the aggregates can be explored. Dr. Buchanan and her group will determine how nanoparticles alter aggregation pathways, with particular focus on determining whether new intermediate species or structural polymorphs are formed. Methods that facilitate better understanding of protein-nanoparticle interactions could be broadly applied in the future to better explain self-assembly of both biological and synthetic polymers into hierarchical structures. 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.