Event
Bioengineering Seminar Series: Rodger McEver
Friday, November 14, 2008
11:00 a.m.
Room 2108, Chemical and Nuclear Engineering Bldg.
Professor Helim Aranda-Espinoza
(301) 405-8250
helim@umd.edu
Force Regulation of Leukocyte and Platelet Adhesion Under Flow
Presented by Rodger McEver
Eli Lilly Distinguished Chair
Cardiovascular Biology Research Program
Oklahoma Medical Research Foundation
University of Oklahoma
During inflammation, flowing leukocytes tether to and roll on activated endothelial cells, then decelerate and arrest before they emigrate into the underlying tissues. During hemorrhage, flowing platelets tether to and roll on damaged subendothelial matrices, then arrest, aggregate, and promote coagulation. Interactions of selectins with glycosylated ligands promote leukocyte rolling, whereas interactions of the platelet GPIb-IX-V complex with von Willebrand factor promote platelet rolling. Rolling requires a minimal flow rate, or shear threshold. As flow drops below this threshold, rolling becomes more rapid and irregular until the cells detach. Shear stress applies force to bonds between adhesion receptors, which affects their lifetimes. As flow increases from suboptimal levels, force first prolongs bond lifetimes (catch bonds) until they reach a maximal level. Further increases in force shorten bond lifetimes (slip bonds). Catch bonds enable flow-enhanced adhesion of leukocytes and platelets to vascular surfaces and may prevent inappropriate agglutination of circulating cells. Potential structural mechanisms for catch bonds will be discussed.
