(Dr. Cheng Zhu, advisor)
"Dissecting Contributions of Structural Elements of PSGL-1 to Its Interaction with P-Selectin Using AFM"
The interaction between P-selectin and its ligand PSGL-1 is an important part of leukocyte recruitment, a critical step of the inflammatory response. The P-selectin/PSGL-1 interaction mediates the earliest phase of leukocyte rolling, the first stage of recruitment.
The ability of the P-selectin/PSGL-1 interaction to mediate leukocyte rolling has been linked to its characteristic binding kinetics, which in turn has been attributed to unique aspects of molecular structure. A recent study by Dr. Bryan T. Marshall characterized the kinetics of P-selectin binding to both dimeric, wild type PSGL-1 (wtPSGL-1) and recombinant, soluble monomeric PSGL-1 (sPSGL-1) using atomic force microscopy (AFM), a technique which excludes many cellular contributions to kinetics measurements. Furthermore, a glycosulfopeptide termed 2-GSP-6 has been developed to display similar solution kinetics with P-selectin, but lack many structural components of PSGL-1. Therefore, the availability of 2-GSP-6 together with the AFM technique provides an opportunity to dissect some of the contributions of PSGL-1 molecular structure to its interaction with P-selectin.
In order to study how PSGL-1 structure influences P-selectin/PSGL-1 kinetics, the kinetics of the 2-GSP-6/P-selectin interaction were measured using atomic force microscopy (AFM) and compared to PSGL-1/P-selectin results by Dr. Marshall. The results revealed differences in measured kinetics which correlate with slight differences in solution kinetics, but not necessarily with the large differences in molecular structure.