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Simultaneous Tether Extraction Contributes to Neutrophil Rolling Stabilization: A Model Study

Department of Biomedical Engineering, Washington University, Saint Louis, Missouri

Correspondence: Address reprint requests to Jin-Yu Shao, PhD, Dept. of Biomedical Engineering, Washington University in St. Louis, Campus Box 1097, Rm. 290E, Whitaker Hall, One Brookings Dr., St. Louis, MO 63130-4899. Tel.: 314-935-7467; Fax: 314-935-7448; E-mail: shao{at}biomed.wustl.edu.

Neutrophil rolling is the initial step of neutrophil recruitment to sites of inflammation. During the rolling, membrane tethers are very likely extracted from both the neutrophil and the endothelial cell lining of vessel walls. Here, we present a two-dimensional neutrophil-rolling model to investigate whether and how membrane tethers contribute to stable neutrophil rolling. In our model, neutrophils are assumed to be rigid spheres covered with randomly distributed deformable microvilli, and endothelial cells are modeled as flat membrane surfaces decorated with evenly distributed ligands. The instantaneous rolling velocity and other unknowns of the model are calculated by coupling the hydrodynamic resistance functions, the geometric relationships, and the constitutive equations that govern microvillus extension and tether extraction. Our results show that glutaraldehyde-fixed neutrophils (without microvillus extension or tether extraction) roll unstably on a P-selectin-coated substrate with large variance in rolling velocity. In contrast, normal neutrophils roll much more stably, with small variance in rolling velocity. Compared with tether extraction from the neutrophil alone, simultaneous tether extraction from the neutrophil and endothelial cell greatly increases the lifetime of the adhesive bond that mediates the rolling, allows more transient tethers to make the transition into stable rolling, and enables rolling neutrophils to be more shear-resistant.

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