Mechanisms and Applications of Protein Analysis by Desorption Electrospray Ionization-Mass Spectrometry (DESI-MS)

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With support from the Chemical Measurement and Imaging program in the Division of Chemistry, Professors Andre Venter and Todd Barkman’s team at Western Michigan University are devising sensitive methods for identifying and characterizing proteins - key building blocks of life. By systematically optimizing sample additives and probe parameters for analysis of proteins in solution and on surfaces, Dr. Venter and his team is not only improving protein analysis, but is also adding to the fundamental understanding of protein solubility and stability, with important potential consequences for bioanalytical measurements, recombinant protein expression, and applications such as the development of protein therapeutics. Students participating in these studies learn about chemistry and biology. In addition, Dr. Venter and colleagues bring the research topics into the classroom, including an unusual interdisciplinary course engaging aspiring scientists with students in the sonic and visual arts. These exposures help prepare both groups for the interdisciplinary nature of STEAM - science, technology, engineering, arts and mathematics - in contemporary society. This research draws on the observation that adding serine either to the spray or to a deposited sample can enhance sensitivity in desorption electrospray ionization (DESI) mass spectrometric analysis of proteins. The underlying mechanism is assessed by studying the effects of derivatization of the serine additive at all three reactive sites. Signals derived from protein monomers and aggregates in native and denatured states are monitored under basic, neutral, and acidic conditions to probe which functional groups and molecular properties drive protein dissolution and stability in solution. Drs. Venter and Barkman are also studying the efficacious effect of adding ethyl acetate vapor to the atmosphere surrounding the analyte, which has been found to increase protein signal intensities and reduce the abundance of spectral features derived from clusters. Better understanding of the mechanisms of these effects may enable novel high-throughput strategies for identification of proteins and their enzymatic functions.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.