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This Article Full Text Full Text (PDF) All Versions of this Article: 295/4/H1439    most recent 91536.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Pawar, P. Articles by Konstantopoulos, K. PubMed PubMed Citation Articles by Pawar, P. Articles by Konstantopoulos, K.

Roles of cell and microvillus deformation and receptor-ligand binding kinetics in cell rolling

¹Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland; ²Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai, India; and ³Department of Mechanical Engineering, University of Maryland, Baltimore, Maryland

Submitted 31 December 2007 ; accepted in final form 13 July 2008

Polymorphonuclear leukocyte (PMN) recruitment to sites of inflammation is initiated by selectin-mediated PMN tethering and rolling on activated endothelium under flow. Cell rolling is modulated by bulk cell deformation (mesoscale), microvillus deformability (microscale), and receptor-ligand binding kinetics (nanoscale). Selectin-ligand bonds exhibit a catch-slip bond behavior, and their dissociation is governed not only by the force but also by the force history. Whereas previous theoretical models have studied the significance of these three "length scales" in isolation, how their interplay affects cell rolling has yet to be resolved. We therefore developed a three-dimensional computational model that integrates the aforementioned length scales to delineate their relative contributions to PMN rolling. Our simulations predict that the catch-slip bond behavior and to a lesser extent bulk cell deformation are responsible for the shear threshold phenomenon. Cells bearing deformable rather than rigid microvilli roll slower only at high P-selectin site densities and elevated levels of shear (400 s^–1). The more compliant cells (membrance stiffness = 1.2 dyn/cm) rolled slower than cells with a membrane stiffness of 3.0 dyn/cm at shear rates >50 s^–1. In summary, our model demonstrates that cell rolling over a ligand-coated surface is a highly coordinated process characterized by a complex interplay between forces acting on three distinct length scales.

immersed boundary method; Monte Carlo simulation; cell adhesion; cell deformation; viscoelastic microvillus; fluid shear; P-selectin