Protein-Surface Interactions: MALDI MS Based Fundamental Studies and Bioselective Probe Development

Southern Illinois University At Carbondale, Carbondale IL

Investigators

Abstract

Professor Gary Kinsel of the University of Texas Arlington is supported by the Analytical and Surface Chemistry Program to systematically explore protein-surface interactions as a fundamental determinant of the performance of matrix assisted laser-desorption/ionization mass spectrometry (MALDI). The PI seeks an understanding of how surface properties affect MALDI and how these properties can be used to enhance its bioanalytical utility. Through the PI's previous CAREER Award, the importance of surface effects on MALDI signal for peptides and proteins has been quantitatively demonstrated, and has lead to the conclusion that the limit of detection (LOD) for MALDI is at least in part regulated by protein-surface interactions. In collaboration with Prof. Richard Timmons, the PI will examine a variety of non-fouling surfaces produced by rf plasma polymerization in an effort to further lower the MALDI LOD. A second conclusion drawn from the CAREER Award results is that surface chemistry can be used to selectively modulate peptide and protein signals. Here, metal impregnated surfaces will be explored as a means to selectively isolate phosphopeptides, which are currently of great interest in the proteomics community. They also propose to use surface charge as a means to concentrate analytes; surface charge can be varied as a function of pH, which will allow for the selection of specific pI fractions to be concentrated and later released for MALDI analysis. MALDI is an important approach for the sequencing of peptides and polymers, but the fundamental processes and factors that affect sensitivity and response are not fully understood. This work will advance the state of the analytical art by improving sensitivity and specificity in MALDI analyses. It will also further develop the interface between materials science and analytical chemistry, by showing how specifically tailored materials and surfaces can be rapidly integrated into analytical methods. Finally, it will continue to develop new tools for the study of protein-surface interactions, which are important in many areas, for example, in the understanding of cell surface biology and the development of biosensors. The practical importance of the proposed program is demonstrated by the industrial support and ongoing industrial collaborations that the PI already has in place for the further development of MALDI MS technology for applications including drug discovery and bioanalytical testing for disease.