Biophysics and Biochemistry of Receptor-Ligand Mediated Adhesion to the Endothelium
The circulatory system consists of blood flowing through an intricate network of blood vessels, whose inner lining is composed of endothelial cells, collectively known as the vascular endothelium. Blood is composed of formed elements (blood cells and platelets) suspended in a saline solution containing dissolved proteins and other solutes. Molecular interactions between receptors expressed on the vascular endothelium and ligands expressed on the formed elements play a critical role in a variety of physiological and pathological processes. Well-known examples include, leukocyte recruitment and platelet deposition at sites of tissue injury, tumor metastasis and atherosclerosis. Since this adhesion occurs in the fluid dynamic environment of circulation, it is paramount to study vascular adhesion from both a biological and an engineering standpoint. There is a distinct possibility that differences in the diameters of formed elements affect their adhesion and consequently, their function. This motivates a study into the role of particle diameter in receptor-ligand mediated adhesion. Our results clearly demonstrate that adhesion is strongly dependent on particle size and provide experimental proof for mathematical models linking particle size to adhesion. The selectin and integrin families of cell adhesion molecules play a key role in orchestrating leukocyte recruitment to sites of inflammation. In a separate study, we examine molecular interactions between the leukocyte integrin Mac-1 (CD11b/CD18), and endothelial cells under flow. Our results reveal that Mac-1 coated microspheres adhere to endothelial cells via E-selectin and an additional mechanism that perhaps involves a yet unidentified endothelial receptor. Motivated by a desire to further the understanding of leukocyte recruitment and hematopoietic progenitor cell (HPC) entry into bone marrow, numerous studies have focused on identifying ligands for E-selectin on a specific HPC cell line, namely HL60 cells. These previous reports both support and refute the ability of HL60 cell expressed P-selectin glycoprotein ligand (PSGL-1) to serve as an E-selectin ligand. Our third study provides evidence that PSGL-1 can, in fact, support attachment of HL60 cells to endothelial E-selectin under flow. Taken together, these three studies contribute to the understanding of the biochemistry and biophysics of receptor-ligand mediated adhesion to the endothelium.
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:biophysics cell adhesion endothelium particle size selectins and integrins
Date of Publication:01/01/2002