Studying Molecular Behavior on Surfaces: From Nanoparticles to Biofilms

Friday, September 6, 2019

Dr. Nicholas Fitzkee

Department of Chemistry

Mississippi State University

Every year, over 1.5 million Americans are affected by a healthcare related infection. The source of many of these infections is an implanted medical device, where bacteria can colonize to form biofilms. During the earliest stages of biofilm formation, proteins and other molecules on the bacterial surface spontaneously adsorb to the medical device, but the molecular determinants of this process are unclear. A related problem occurs in the design of functionalized nanoparticles, where nanoparticles are engineered for therapeutic and biosensing applications. Spontaneous adsorption of host proteins to nanoparticle surfaces can interfere with the desired nanoparticle function, potentially negating their utility. While many biophysical approaches have been applied to understanding protein behavior on surfaces, NMR offers unique advantages because of its ability to monitor the environment of individual chemical groups. We have developed a suite of NMR experiments for characterizing protein structure, orientation, and function on the surface of nanoparticles. In this talk, I will present our lab’s progress on studying protein behavior on surfaces. Our work indicates that proteins directly adsorbed to nanoparticle surfaces tend to be globular and form a single monolayer of protein. Intrinsically disordered and unstable proteins do not follow this trend, suggesting that adsorption modulates protein stability. Hydrogen-deuterium exchange (HDX) and methyl labeling have been used to characterize the structure and orientation of a small, 6 kDa protein on a gold nanoparticle surface, revealing for the first time structural insights into the hard corona. More recently, we have investigated the adsorption behavior of the R2ab domain of autolysin E, a protein implicated in staphylococcal attachment to surfaces. This protein appears to behave similarly to other proteins, and current work is focused on investigating R2ab’s behavior on polystyrene and silica nanoparticle surfaces.

Dr. Nicholas Fitzkee is an associate professor in the Department of Chemistry at Mississippi State University. He earned his Ph.D. in Biophysics from Johns Hopkins University with Dr. George Rose, and he completed a postdoc at the National Institutes of Health with Dr. Ad Bax. Dr. Fitzkee is broadly interested in using NMR spectroscopy to study the molecular basis of protein adsorption to surfaces. His group works to develop novel, NMR-based techniques for understanding protein-surface interactions. A major goal of his research is developing predictive physical models for understanding protein adsorption. Such models could be used to control protein adsorption in biological sensors and medical devices.

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