Molecular dynamics of the transition from L-selectin- to β2-integrin- dependent neutrophil adhesion under defined hydrodynamic shear

A. D. Taylor, S. Neelamegham, J. D. Hellums, C. W. Smith, S. I. Simon

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

Homotypic adhesion of neutrophils stimulated with chemoattractant is analogous to capture on vascular endothelium in that both processes depend on L-selectin and β2-integrin adhesion receptors. Under hydrodynamic shear, cell adhesion requires that receptors bind sufficient ligand over the duration of intercellular contact to withstand hydrodynamic stresses. Using cone-plate viscometry to apply a uniform linear shear field to suspensions of neutrophils, we conducted a detailed examination of the effect of shear rate and shear stress on the kinetics of cell aggregation. A collisional analysis based on Smoluchowski's flocculation theory was employed to fit the kinetics of aggregation with an adhesion efficiency. Adhesion efficiency increased with shear rate from ~20% at 100 s-1 to ~80% at 400 s-1. The increase in adhesion efficiency with shear was dependent on L-selectin, and peak efficiency was maintained over a relatively narrow range of shear rates (400- 800 s-1) and shear stresses (4-7 dyn/cm2). When L-selectin was blocked with antibody, β2-integrin (CD11a, b) supported adhesion at low shear rates (< 400 s-1). The binding kinetics of selectin and integrin appear to be optimized to function within discrete ranges of shear rate and stress, providing an intrinsic mechanism for the transition from neutrophil tethering to stable adhesion.

Original languageEnglish (US)
Pages (from-to)3488-3500
Number of pages13
JournalBiophysical Journal
Volume71
Issue number6
StatePublished - Dec 1996
Externally publishedYes

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L-Selectin
Hydrodynamics
Molecular Dynamics Simulation
Integrins
Neutrophils
Flocculation
Selectins
Cell Aggregation
Chemotactic Factors
Vascular Endothelium
Cell Adhesion
Suspensions
Ligands
Antibodies
adhesion receptor

ASJC Scopus subject areas

  • Biophysics

Cite this

Taylor, A. D., Neelamegham, S., Hellums, J. D., Smith, C. W., & Simon, S. I. (1996). Molecular dynamics of the transition from L-selectin- to β2-integrin- dependent neutrophil adhesion under defined hydrodynamic shear. Biophysical Journal, 71(6), 3488-3500.

Molecular dynamics of the transition from L-selectin- to β2-integrin- dependent neutrophil adhesion under defined hydrodynamic shear. / Taylor, A. D.; Neelamegham, S.; Hellums, J. D.; Smith, C. W.; Simon, S. I.

In: Biophysical Journal, Vol. 71, No. 6, 12.1996, p. 3488-3500.

Research output: Contribution to journalArticle

Taylor, AD, Neelamegham, S, Hellums, JD, Smith, CW & Simon, SI 1996, 'Molecular dynamics of the transition from L-selectin- to β2-integrin- dependent neutrophil adhesion under defined hydrodynamic shear', Biophysical Journal, vol. 71, no. 6, pp. 3488-3500.
Taylor, A. D. ; Neelamegham, S. ; Hellums, J. D. ; Smith, C. W. ; Simon, S. I. / Molecular dynamics of the transition from L-selectin- to β2-integrin- dependent neutrophil adhesion under defined hydrodynamic shear. In: Biophysical Journal. 1996 ; Vol. 71, No. 6. pp. 3488-3500.
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