The Prell laboratory uses state-of-the-art mass spectrometry and ion mobility techniques to investigate the physical and chemical properties that govern the organization of macromolecular assemblies at the nanoscale, including those found in biological membranes. At the scale of a few nanometers, chemical interactions (from covalent bonds to hydrogen bonds and van der Waals interactions) collectively give rise to material properties, such as surface tension, viscosity, and phase separation behavior, in many condensed phase "soft-matter" systems. Biological cells, for instance, likely exploit delicate balances of these interactions to regulate signalling, endocytosis, and many other processes, although a precise characterization of the nanoscale structures that are involved can be extremely challenging. Mass spectrometry and allied techniques have proved invaluable for studying the structure and organization of many kinds of matter, from simple molecules to megadalton-sized cytosolic and even membrane protein assemblies. Our lab uses newly developed methods capable of transferring and analyzing intact macromolecular assemblies in the gas phase while retaining much of their condensed-phase tertiary and quaternary structure. We learn complementary information about their composition, shape, and folding state in these same experiments using ion mobility spectrometry. Combined with computational modeling and results from other bioanalytical experiments, data obtained with these methods can be used to construct detailed models of the assemblies, ligand binding, and other properties. Assembly structures and their dependence on the condensed-phase environment in which they arise enable us to paint a vivid picture of how biological and other nanoscale systems bridge the gap from chemical to material properties, with a view toward biochemical, pharmaceutical, and technological applications. These experiments are informed by our in-house Fourier Transform-based spectral analysis tools (iFAMS), collisional cross section modeling software (Collidoscope), and MD simulations of ion heating, unfolding, and dissociation. iFAMS and Collidoscope are available by request as well as on Github as open-source, free, publicly available software (see github.com/prellgoup/Collidoscope and github.com/seanpatcleary/iFAMS). Our research is supported generously by the National Institute of Allergy and Infectious Disease, National Science Foundation CAREER Award, and an American Society for Mass Spectrometry Research Award.
Ph.D., University of California, Berkeley, Chemistry