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| Content Provider | IEEE Xplore Digital Library |
|---|---|
| Author | Doggett, T.A. Girdhar, G. Lawshe, A. Schmidtke, D.W. Laurenzi, I.J. Diamond, S.L. Diacovo, T.G. |
| Copyright Year | 2002 |
| Description | Author affiliation: Dept. of Pediatrics & Pathology, Washington Univ., St. Louis, MO, USA (Doggett, T.A.; Girdhar, G.; Lawshe, A.) |
| Abstract | The ability of platelets to tether to and translocate on injured vascular endothelium relies on the interaction between the platelet glycoprotein receptor Ib alpha (GPIb/spl alpha/) and the A1 domain of von Willebrand factor (vWF-A1). We now report that the GPIb/spl alpha/-vWF-A1 tether bond displays similar kinetic attributes as the selectins including: 1) the requirement for a critical level of flow to initiate adhesion, 2) short-lived tethering events at sites of vascular injury in vivo, and 3) a fast intrinsic dissociation rate constant, k/sub off//sup 0/ (3.45 /spl plusmn/ 0.37 s/sup -1/). Values for k/sub off/, also varied exponentially (4.2 /spl plusmn/ 0.8 s/sup -1/ to 7.3 /spl plusmn/ 0.4 s/sup -1/) as a function of the force applied to the bond (from 36 to 217pN). The biological importance of rapid bond dissociation is demonstrated by kinetic characterization of the naturally occurring A1 domain mutation, I546V that results in spontaneous binding of plasma vWF to circulating platelets in flowing blood. This mutation resulted in a loss of the shear threshold phenomenon, a /spl sim/6-fold reduction in k/sub off/, but no significant alteration in the ability of the tether bond to resist shear-induced forces. Thus, flow dependent adhesion and rapid and force-dependent kinetic properties are the predominant features of the GPIb/spl alpha/-vWF-A1 tether bond. |
| Starting Page | 349 |
| Ending Page | 350 |
| File Size | 132686 |
| Page Count | 2 |
| File Format | |
| ISBN | 0780376129 |
| ISSN | 1094687X |
| DOI | 10.1109/IEMBS.2002.1134529 |
| Language | English |
| Publisher | Institute of Electrical and Electronics Engineers, Inc. (IEEE) |
| Publisher Date | 2002-10-23 |
| Publisher Place | USA |
| Access Restriction | Subscribed |
| Rights Holder | Institute of Electrical and Electronics Engineers, Inc. (IEEE) |
| Subject Keyword | Kinetic theory Biomechanics Adhesives Bonding forces Genetic mutations Displays Injuries In vivo Plasmas Blood |
| Content Type | Text |
| Resource Type | Article |
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