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

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Title Roles of cell and microvillus deformation and receptor-ligand binding kinetics in cell rolling
 
Creator PAWAR, P
JADHAV, S
EGGLETON, CD
KONSTANTOPOULOS, K
 
Subject selectin glycoprotein ligand-1
adhesive dynamics simulations
p-selectin
shear-flow
endothelial glycocalyx
leukocyte deformation
human neutrophils
bond
surfaces
deformability
immersed boundary method
monte carlo simulation
cell adhesion
cell deformation
viscoelastic microvillus
fluid shear
p-selectin
 
Description 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 (membrane 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.
 
Publisher AMER PHYSIOLOGICAL SOC
 
Date 2011-07-17T01:30:53Z
2011-12-26T12:50:02Z
2011-12-27T05:35:59Z
2011-07-17T01:30:53Z
2011-12-26T12:50:02Z
2011-12-27T05:35:59Z
2008
 
Type Article
 
Identifier AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 295(4), H1439-H1450
0363-6135
http://dx.doi.org/10.1152/ajpheart.91536.2007
http://dspace.library.iitb.ac.in/xmlui/handle/10054/4580
http://hdl.handle.net/10054/4580
 
Language en