Title: New Frontiers in Mass Spectrometry: Biomolecular Ion Structures, Thermochemistry, and Imaging
Abstract: Native ion mobility-mass spectrometry (IM-MS) aims to reveal structural information about biomolecules and their complexes, including and especially those that frustrate conventional techniques. One of the most common ways to access information beyond ion mass and charge in native IM-MS is to subject ions to hundreds to thousands of high-energy collisions with buffer gas, which can cause the ions to unfold (“Collision Induced Unfolding”, CIU) or dissociate (“Collision Induced Dissociation”, CID). Here, we apply our recently developed IonSPA software to determine thermochemical barriers encountered in CIU and CID of native protein ions. To date, CIU has been used largely to empirically characterize differences in structure between closely related proteins, such as innovator biologics and their biosimilars. A deeper view into biomolecular ion structure has been difficult to obtain with CIU in part due to the unclear relationship between the acceleration potential applied to the ions and their corresponding change in internal energy. With IonSPA, the internal energy (and temperature) of ions in CIU as a function of time can be straightforwardly modeled and used to determine enthalpy and entropy barriers for each unfolding step in the CIU “fingerprints” of several protein and protein complex ions. These thermochemical data are important for interpreting CIU fingerprints in terms of native ion structure.
Another important, emerging application of IM-MS is imaging of intact proteins in biological tissues. Nanospray desorption electrospray ionization mass spectrometry imaging (nanoDESI MSI), developed by our collaborators in the Laskin Group at Purdue University, can map and quantitate proteins down to few-micron resolution, but a large, sample-dependent background of unresolved protein ions can frustrate interpretation of nanoDESI MSI data. We show here how data analysis tools developed in the Prell Group for native IM-MS can be used to disentangle highly heterogeneous protein MSI data and subtract unresolved background for accurate pixel-by-pixel quantitation.
Bio: Associate Professor James Prell received a bachelor’s degree in Mathematics, Chemistry, and German, with minors in Music and Religious Studies, from Washington University in St. Louis in 2005. He received his PhD from the University of California, Berkeley, in 2011, where he was advised by Prof. Evan Williams. He completed a postdoc at UC Berkley with Prof. Stephen Leone, after which he joined the Chemistry faculty at the University of Oregon in 2014. He received an NSF CAREER Award and an American Society for Mass Spectrometry Research Award in 2018. His research focuses on fundamentals of native ion mobility-mass spectrometry as well as development of advanced computational resources for interpretation of mass spectrometry data and analyte quantitation.