With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Zhan Chen and his group at the University of Michigan are developing an innovative approach to elucidate detailed molecular structures of surface-bound proteins. Their approach uses selective heavy-atom (isotope) labeling and advanced spectroscopic methods to derive crucial knowledge about how adsorption of proteins at interfaces affects their structure and function. These interactions impact a range of applications, such as biocompatibility of biomedical materials, performance of antifouling coatings, selectivity and sensitivity of biosensors, and efficiency of biofuel cells. This highly interdisciplinary research provides educational opportunities for graduate and undergraduate students. Professor Chen and his students are also working to engage high school students (including those from underrepresented groups, including women) and to enhance their interest in science through a class taught each summer.
This project focuses on the development of a generally applicable methodology to characterize the conformation and orientation of proteins at interfaces using isotope labeling and sum frequency generation (SFG) vibrational spectroscopy. Using a model cell membrane-associated antimicrobial peptide tachyplesin I, a protein GB1 mutant which can retain its native structure at the graphene interface, and a wild-type protein GB1 which denatures on graphene, Professor Chen and his group are developing SFG isotope labeling methods to characterize various protein secondary structures at the solid/liquid interface; to deduce orientations and slight conformation changes of interfacial proteins from crystal structures due to interfacial interactions; and to determine conformations of denatured interfacial proteins. Results obtained from molecular dynamics simulations and the Hamiltonian approach are compared to the experimentally measured SFG data from isotopically labeled proteins to determine the most likely protein conformations and orientations at the interface. This method can also be used to determine interfacial structures of proteins with unknown crystal structures, adding a powerful spectroscopic tool for studying interfacial biological molecules.
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.
