Modeling the reversible kinetics of neutrophil aggregation under hydrodynamic shear

Sriram Neelamegham, Andrew D. Taylor, J. David Hellums, Micah Dembo, C. Wayne Smith, Scott I. Simon

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Abstract

Neutrophil emigration into inflamed tissue is mediated by β2-integrin and L-selectin adhesion receptors. Homotypic neutrophil aggregation is also dependent on these molecules, and it provides a model system in which to study adhesion dynamics. In the current study we formulated a mathematical model for cellular aggregation in a linear shear field based on Smoluchowski's two-body collision theory. Neutrophil suspensions activated with chemotactic stimulus and sheared in a cone-plate viscometer rapidly aggregate. Over a range of shear rates (400-800 s-1), ~90% of the single cells were recruited into aggregates ranging from doublets to groupings larger than sextuplets. The adhesion efficiency fit to these kinetics reached maximum levels of >70%. Formed aggregates remained intact and resistant to shear up to 120 s, at which time they spontaneously dissociated back to singlets. The rate of cell disaggregation was linearly proportional to the applied shear rate, and it was ~60% lower for doublets as compared to larger aggregates. By accounting for the time-dependent changes in adhesion efficiency, disaggregation rate, and the effects of aggregate geometry, we succeeded in predicting the reversible kinetics of aggregation over a wide range of shear rates and cell concentrations. The combination of viscometry with flow cytometry and mathematical analysis as presented here represents a novel approach to differentiating between the effects of hydrodynamics and the intrinsic biological processes that control cell adhesion.

Original languageEnglish (US)
Pages (from-to)1527-1540
Number of pages14
JournalBiophysical Journal
Volume72
Issue number4
StatePublished - Apr 1997
Externally publishedYes

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ASJC Scopus subject areas

  • Biophysics

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Neelamegham, S., Taylor, A. D., Hellums, J. D., Dembo, M., Smith, C. W., & Simon, S. I. (1997). Modeling the reversible kinetics of neutrophil aggregation under hydrodynamic shear. Biophysical Journal, 72(4), 1527-1540.