Conformational Proteomics on Nanoparticle Surfaces

University Of Illinois At Urbana-Champaign, Urbana IL

Investigators

Abstract

In this project funded by the Macromolecular, Supramolecular, and Nanoscience program of the Chemistry Division, Professor Catherine Murphy of the University of Illinois at Urbana-Champaign addresses the conformation (three-dimensional shape) of proteins on nanoparticle surfaces as a function of nanoparticle size, shape, and surface chemistry. Insights from these experiments may lead to improved prediction of biological effects at the molecular and potentially cellular levels. Metallic nanoparticles in the 10-100 nm size range exhibit unusual properties that enable applications in biology, ranging from diagnostics to therapeutics. The details of the chemistry at the surface of these nanoparticles matter. Some surface chemistries promote protein binding. Others discourage protein binding, and some even control how proteins bind to the surface. The position of molecules such as proteins on the surface of nanoparticles can influence the fate and function of these nanoparticles in biological systems. The project also contributes to the education and training of undergraduate and graduate students in the areas of nanotechnology, bionanotechnology, and analytical measurements. This training provides a pipeline of well-rounded scientists who contribute to the innovation economy. Classroom modules on surface chemistry are created and broadly disseminated to enable students to learn about these scientific topics. Outreach to non-science students helps educate non-scientists about bionanotechnology as well as improve the communication skills of the science students. A wide-ranging set of experiments are designed to examine the phenomenon of "conformational proteomics on nanoparticles." This research group is developing the ability to measure protein conformations and then rationally alter the conformation/orientation of proteins on nanoparticle surfaces. The systems include gold cores with various organic ligand shells or new porous, constraining shells. The proteins include a small, carefully selected set of molecules with intrinsically interesting bioactivity. The methods used include adaptive control of protein behavior that comes from "plasmonic refreshing" of the surface or capturing protein conformers in designed pores near the metal surface. The measurement of bound protein conformation and orientation comes from a combination of NMR methods, footprinting mass spectrometry, and vibrational spectroscopy.