Biophysical and Biochemical Characterization of Receptor-Ligand Interactions:

Selectin/ligand-mediated cellular interactions play a pivotal roles in cancer metastasis, inflammation and thrombosis. Characterizing the biophysical and biochemical nature of selectin/ligands will therefore provide a basis for designing potent, specific selectin ligand antagonists to combat the aforementioned pathological processes.

Using single molecule force spectroscopy, we probe in situ the kinetic and mechanical properties of single selectin molecules binding to single ligands on intact human leukocytes and carcinoma cells. We are currently extracting and purifying selectin/ligands from vascular and tumor cells by using novel and standard biochemistry techniques.

Select Publications:

S.L. Napier, Z.R. Healy, R.L. Schnaar, K. Konstantopoulos, "Selectin Ligand Expression Regulates the Initial Vascular Interactions of Colon Carcinoma Cells: The Roles of CD44v and Alternate Sialofucosylated Selectin Ligands", Journal of Biological Chemistry 282(6); 3433-3441, 2007. html

P. Panorchan, M.S. Travis, K. Davis, Y. Tseng, K. Konstantopoulos, D. Wirtz, "Single-Molecule Analysis of Cadherin-mediated Cell-Cell Adhesion", Journal of Cell Science 119(Pt1); 66-74, 2006 Jan 1. html

W.D. Hanley, S. Napier, M.M. Burdick, R.L. Schnaar, R. Sackstein, K. Konstantopoulos, "Variant CD44 Isoforms are the P- and L- Selectin Ligands on Colon Carcinomas", The FASEB Journal. Published electronically 2005 Dec 13. html

W.D. Hanley, M.M. Burdick, K. Konstantopoulos, and R. Sackstein, "CD44 on LS174T Colon Carcinoma Cells Possesses E-Selectin Ligand Activity." Cancer Research. 65(13):5812-7, 2005. html

W.D. Hanley, D. Wirtz, K. Konstantopoulos, “Distinct Kinetic and Mechanical Properties Govern Selectin-Leukocyte Interactions”, Journal of Cell Science 117(12); 2503-2511, 2004. html

W.D. Hanley, O.J.-T. McCarty, S. Jadhav, Y. Tseng, D. Wirtz, and K. Konstantopoulos, “Single-Molecule Characterization of P-selectin/Ligand Binding” Journal of Biological Chemistry 278(12); 10556-10661, 2003. html

M.M. Burdick, R.L. Schnaar, B.E. Collins, B.S. Bochner, K. Konstantopoulos, “Glycolipids Support E-selectin-Specific Strong Cell Tethering under Flow”, Biochemical and Biophysical Research Communications 284(1); 42-49, 2001.  html

 

 

A Schematic of a Molecular Force Probe.