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Transport Governs Flow-Enhanced Cell Tethering through L-Selectin at Threshold Shear

Tadayuki Yago ^*, Veronika I. Zarnitsyna , Arkadiusz G. Klopocki ^*, Rodger P. McEver ^*  and Cheng Zhu  

^* Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia; Department of Biochemistry and Molecular Biology, Oklahoma Center for Medical Glycobiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; and Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia

Correspondence: Address reprint requests to Cheng Zhu, Coulter Dept. of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0363. Tel.: 404-894-3269; Fax. 404-385-1397; E-mail: cheng.zhu{at}me.gatech.edu; or to Rodger McEver, Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, 825 NE 13th St., Oklahoma City, OK 73104. Tel.: 405-271-6480; Fax: 405-271-3137; E-mail: rodger-mcever{at}omrf.ouhsc.edu.

Flow-enhanced cell adhesion is a counterintuitive phenomenon that has been observed in several biological systems. Flow augments L-selectin-dependent adhesion by increasing the initial tethering of leukocytes to vascular surfaces and by strengthening their subsequent rolling interactions. Tethering or rolling might be influenced by physical factors that affect the formation or dissociation of selectin-ligand bonds. We recently demonstrated that flow enhanced rolling of L-selectin-bearing microspheres or neutrophils on P-selectin glycoprotein ligand-1 by force decreased bond dissociation. Here, we show that flow augmented tethering of these microspheres or cells to P-selectin glycoprotein ligand-1 by three transport mechanisms that increased bond formation: sliding of the sphere bottom on the surface, Brownian motion, and molecular diffusion. These results elucidate the mechanisms for flow-enhanced tethering through L-selectin.

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