Abstract
P-selectin glycoprotein ligand-1 (PSGL-1) binding to P-selectin mediates leukocyte rolling under conditions of flow. In human neutrophils, a type of leukocyte belonging to the innate immune system, PSGL-1 molecules are located on the neutrophil's surface ruffles, called microvilli. Each newly formed P-selectin-PSGL-1 bond can become load bearing, imposing on its microvillus a pulling force that deforms the microvillus. Depending on the magnitude of the bond force, a microvillus can be extended, or a thin membrane cylinder (a tether) can be formed at the tip of the microvillus. Here we propose a Kelvin-Voigt viscoelastic material as an improved model for microvillus extension. Using a modified version of our Event-Tracking Model of Adhesion (ETMA), we demonstrate how P-selectin-PSGL-1 load-bearing bonds shape microvillus deformation during neutrophil rolling at low shear (wall shear rate of 50 s-1, P-selectin site density of 150 molecules μm -2). We also discuss the impact of microvillus deformability on neutrophil rolling. We find that the average microvillus extension constitutes 65% of the total microvillus-tether complex extension, and that the rolling neutrophil may never fully rest. A quantitative comparison with the corresponding non-deformable microvilli case supports a concept that the ability of the microvillus to deform stabilizes cell rolling.
Original language | English (US) |
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Pages (from-to) | 207-217 |
Number of pages | 11 |
Journal | Cellular and Molecular Bioengineering |
Volume | 2 |
Issue number | 2 |
DOIs | |
State | Published - Jun 2009 |
Externally published | Yes |
Keywords
- ETMA
- Kelvin-Voigt
- Leukocyte rolling
- Microvillus deformation
- Microvillus elongation
- Microvillus tether
- Modeling of cell rolling
- Neutrophil
- P-selectin
- PSGL-1
ASJC Scopus subject areas
- Modeling and Simulation
- General Biochemistry, Genetics and Molecular Biology