Skip to main content
SpringerLink
Log in

Multi-scale simulation of L-selectin–PSGL-1-dependent homotypic leukocyte binding and rupture

  • Original Paper
  • Published:
Biomechanics and Modeling in Mechanobiology Aims and scope Submit manuscript

Abstract

L-selectin–PSGL-1-mediated polymorphonuclear (PMN) leukocyte homotypic interactions potentiate the extent of PMN recruitment to endothelial sites of inflammation. Cell–cell adhesion is a complex phenomenon involving the interplay of bond kinetics and hydrodynamics. As a first step, a 3-D computational model based on the Immersed Boundary Method is developed to simulate adhesion-detachment of two PMN cells in quiescent conditions. Our simulations predict that the total number of bonds formed is dictated by the number of available receptors (PSGL-1) when ligands (L-selectin) are in excess, while the excess amount of ligands influences the rate of bond formation. Increasing equilibrium bond length results in a higher number of receptor–ligand bonds due to an increased intercellular contact area. On-rate constants determine the rate of bond formation, while off-rates control the average number of bonds by modulating bond lifetimes. Application of an external pulling force leads to time-dependent on- and off-rates and causes bond rupture. Moreover, the time required for bond rupture in response to an external force is inversely proportional to the applied load and decreases with increasing off-rate.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Alon R, Hammer DA, Springer TA (1995) Lifetime of the P-selectin-carbohydrate bond and its response to tensile force in hydrodynamic flow. Nature 374: 539–542

    Article  Google Scholar 

  • Alon R, Fuhlbrigge RC, Finger ER, Springer TA (1996) Interactions through L-selectin between leukocytes and adherent leukocytes nucleate rolling adhesions on selectins and VCAM-1 in shear flow. J Cell Biol 135(3): 849–865

    Article  Google Scholar 

  • Bargatze RF, Kurk S, Butcher EC, Jutila MA (1994) Neutrophils roll on adherent netrophils bond to cytokine-induced endothelial cells via L-selectin on rolling cells. J Exp Med 180: 1785–1792

    Article  Google Scholar 

  • Bell GI (1978) Models for the specific adhesion of cells to cells. Science 200: 618–627

    Article  Google Scholar 

  • Bruehl RE, Springer TA, Bainton DF (1996) Quantification of L-selectin distribution on human leukocyte microvilli by immunogold labeling and electron microscopy. J Histochem Cytochem 44(8): 835–844

    Google Scholar 

  • Charrier JM, Shrivastava S, Wu R (1989) Free and constrained inflation of elastic membranes in relation to thermoforming non-axisymmetric problems. J Strain Anal 24(2): 55–74

    Article  Google Scholar 

  • Chen S, Springer TA (1999) An automatic braking system that stabilizes leukocyte rolling by an increase in selectin bond number with shear. J Cell Biol 144: 185–200

    Article  Google Scholar 

  • Chen W, Zarnitsyna VI, Sarangapani KK, Huang J, Zhu C (2008) Measuring receptor-ligand binding kinetics on cell surfaces: from adhesion frequency to thermal fluctuation methods. Cell Mol Bioeng 1(4): 276–288

    Article  Google Scholar 

  • Chesla SE, Selvaraj P, Zhu C (1998) Measuring two-dimensional receptor-ligand binding kinetics by micropipette. Biophys J 75: 1553–1572

    Article  Google Scholar 

  • Cozen-Roberts C, Lauffenburger DA, Quinn JA (1990) Receptor- mediated cell attachment and detachment kinetics. I. Probabilistic model and analysis. Biophys J 58: 841–856

    Article  Google Scholar 

  • Dembo M (1994) On peeling an adherent cell from a surface. In: vol 24 of series: Lectures on Mathematics in the Life Sciences, Some Mathematical Problems in Biology. American Mathematical Society, Providence, RI. pp 51–77

  • Eggleton CD, Popel AS (1998) Large deformation of red blood cell ghosts in a simple shear flow. Phys Fluids 10: 1834–1845

    Article  Google Scholar 

  • Evans E, Ritchie K (1997) Dynamic strength of molecular adhesion bonds. Biophys J 72: 1541–1555

    Article  Google Scholar 

  • Evans EA, Leung A, Hammer D, Simon S (2001) Chemically distinct transition states govern rapid dissociation of single L-selectin bonds under force. Proc Natl Acad Sci 98(7): 3784–3789

    Article  Google Scholar 

  • Evans EA, Calderwood DA (2007) Forces and bond dynamics in cell adhesion. Science 316: 1148–1153

    Article  Google Scholar 

  • Fritz J, Katopodis AG, Kolbinger F, Anselmetti D (1998) Force- mediated kinetics of single P-selectin/ligand complexes observed by atomic force microscopy. Proc Natl Acad Sci 95: 12283–12288

    Article  Google Scholar 

  • Girdhar G, Shao J-Y (2007) Simultaneous tether extraction from endothelial cells and leukocytes: observation, mechanics, and significance. Biophys J 93: 4041–4052

    Article  Google Scholar 

  • Goldsmith HL, Quinn TA, Drury G, Spanos C, McIntosh FA, Simon SI (2001) Dynamics of neutrophil aggregation in Couette flow revealed by videomicroscopy: effect of shear rate on two-body collision efficiency and doublet lifetime. Biophys J 81: 2020– 2034

    Article  Google Scholar 

  • Guo S, Ray C, Kirkpatrick A, Lad N, Akhremitchev BB (2008) Effects of multiple-bond ruptures on kinetic parameters extracted from force spectroscopy measurements: revisiting biotin-streptavidin interactions. Biophys J 95: 3964–3976

    Article  Google Scholar 

  • Guo S, Lad N, Ray C, Akhremitchev BB (2009) Association kinetics from single molecule force spectroscopy measurements. Biophys J 96: 3412–3422

    Article  Google Scholar 

  • Hammer DA, Apte SM (1992) Simulation of cell rolling and adhesion on surfaces in shear flow: general results and analysis of selectin-mediated neutrophil adhesion. Biophys J 63: 35–57

    Article  Google Scholar 

  • Hinterdorfer P, Baumgartner W, Gruber HJ, Schilcher K, Schindler H (1996) Detection and localization of individual antibody-antigen recognition events by atomic force microscopy. PNAS 93: 3477–3481

    Article  Google Scholar 

  • Jadhav S, Eggleton CD, Konstantopoulos K (2005) A 3-D computational model predicts that cell deformation affects selectin-mediated leukocyte rolling. Biophy J 88: 96–104

    Article  Google Scholar 

  • Jadhav S, Chan KY, Eggleton CD, Konstantopoulos K (2007) Shear modulation of intercellular contact area between two deformable cells colliding under flow. J Biomech 40: 2891–2897

    Article  Google Scholar 

  • Kadash KE, Lawrence MB, Diamond SL (2004) Neutrophil string formation: hydrodynamic thresholding and cellular deformation during cell collisions. Biophys J 86: 4030–4039

    Article  Google Scholar 

  • Khismatullin DB, Truskey GA (2005) Three-dimensional numerical simulation of receptor-mediated leukocyte adhesion to surfaces: effects of cell deformability and viscoelasticity. Phys Fluids 17: 031505

    Article  Google Scholar 

  • Konstantopoulos K, Kukreti S, McIntire LV (1998) Biomechanics of cell interactions in shear fields. Adv Drug Deliv Rev 33: 141–164

    Article  Google Scholar 

  • Kuhner F, Costa LT, Bisch PM, Thalhammer S, Heckl WM, Gaub HE (2004) LexA-DNA bond strength by single molecule force spectroscopy. Biophys J 87: 2683–2690

    Article  Google Scholar 

  • Lasky LA (1992) Selectins: interpreters of cell-specific carbohydrate information during inflammation. Science 258: 964–969

    Article  Google Scholar 

  • Lawrence MB, Springer TA (1991) Leukocytes roll on a selectin at physiologic flow rates: distinction from the prerequisite for adhesion through integrins. Cell 65: 859–873

    Article  Google Scholar 

  • Marshall BT, Sarangapani KK, Wu J, Lawrence MB, McEver RP (2006) Measuring molecular elasticity by atomic force microscope cantilever fluctuations. Biophys J 90: 681–692

    Article  Google Scholar 

  • Merkel R, Nassoy P, Leung A, Ritchie K, Evans E (1999) Energy landscapes of receptor-ligand bonds explored with dynamic force spectroscopy. Nature 397: 50–53

    Article  Google Scholar 

  • Moore KL, Varki A, McEver RP (1991) GMP-140 binds to a glycoprotein receptor on human neutrophils: evidence for a lectin-like interaction. J Cell Biol 112: 491–499

    Article  Google Scholar 

  • Moore KL, Patel KD, Bruehl RE, Li F, Johnson DA, Lichenste HS, Cummings RD, Bainton DF, McEver RP (1995) P-selectin glycoprotein ligand-1 mediates rolling of human neutrophils on P-selectin. J Cell Biol 128: 661–671

    Article  Google Scholar 

  • Mustard JF, Packham MA, Kinlough-Rathbone RL, Perry DW, Regoeczi E (1978) Fibrinogen and ADP-induced platelet aggregation. Blood 52: 453–466

    Google Scholar 

  • Neelamegham S, Taylor AD, Shankaran H, Smith CW, Simon SI (2000) Shear and time-dependent changes in Mac-1, LFA-1, and ICAM-3 binding regulate neutrophil homotypic adhesion. J Immunol 164: 3798–3805

    Google Scholar 

  • Nicolson GL (1988) Organ specificity of tumor metastasis: role of preferential adhesion, invasion and growth of malignant cells at specific secondary sites. Cancer Metastasis Rev 7: 143–188

    Article  Google Scholar 

  • Osborn L (1990) Leukocyte adhesion to endothelium in inflammation. Cell 62: 3–6

    Article  Google Scholar 

  • Paschall CD, Guilford WH, Lawrence MB (2008) Enhancement of L-selectin, but not P-selectin, bond formation frequency by convective flow. Biophys J 94: 1034–1045

    Article  Google Scholar 

  • Patel KD, Nollert MU, McEver RP (1995) P-selectin must extend a sufficient length from the plasma membrane to mediate rolling of neutrophils. J Cell Biol 131(6): 1893–1902

    Article  Google Scholar 

  • Pawar P, Jadhav S, Eggleton CD, Konstantopoulos K (2008) Roles of cell and microvillus deformation and receptor-ligand binding kinetics in cell rolling. Am J Physiol Heart Circ Physiol 295: H1439–H1450

    Article  Google Scholar 

  • Pereverzev YV, Prezhdo OV, Forero M, Sokurenko EV, Thomas WE (2005) The two-pathway model for the catch-slip transition in biological adhesion. Biophys J 89: 1446–1454

    Article  Google Scholar 

  • Peskin CS, McQueen DM (1989) A three dimensional computational method for blood flow in the heart. I. Immersed elastic fibers in a viscous incompressible fluid. J Comput Phys 81: 372

    Article  MathSciNet  MATH  Google Scholar 

  • Puri KD, Finger EB, Springer TA. (1997) The faster kinetics of L-selectin than of E-selectin and P-selectin rolling at comparable binding strength. J Immunol 158: 405–413

    Google Scholar 

  • Rinko LJ, Lawrence MB, Guilford WH (2004) The molecular mechanics pf P- and L-selectin lectin domains binding to PSGL-1. Biophys J 86: 544–554

    Article  Google Scholar 

  • Shao JY, Xu JB (2002) A modified micropipette aspiration technique and its application to tether formation from human neutrophils. J Biomech Eng-T ASME 124: 388–396

    Article  Google Scholar 

  • Shao JY, Ting-Beall HP, Hochmuth RM (1998) Static and dynamic lengths of neutrophil microvilli. Proc Natl Acad Sci USA 95: 6797–6802

    Article  Google Scholar 

  • Shrivastava S, Tang J (1993) Large deformation finite element analysis of non-linear viscoelastic membranes with reference to thermoforming. J Strain Anal 28(1): 31–51

    Article  Google Scholar 

  • Simon SI, Green CE (2005) Molecular mechanics and dynamics of leukocyte recruitment during inflammation. Annu Rev Biomed Eng 7: 151–185

    Article  Google Scholar 

  • Tandon P, Diamond SL (1998) Kinetics of β 2-integrin and L-selectin bonding during neutrophile aggregation in shear flow. Biophys J 75: 3163–3178

    Article  Google Scholar 

  • Taylor AD, Neelamegham S, Hellums JD, Smith CW, Simon SI (1996) Molecular dynamics of the transition from L-selectin to β 2-integrin dependent neutrophil adhesion under defined hydrodynamic shear. Biophys J 71: 3488–3500

    Article  Google Scholar 

  • Tolentino TP, Wu J, Zarnitsyna VI, Fang Y, Dustin ML, Zhu C (2008) Measuring diffusion and binding kinetics by contact area FRAP. Biophys J 95: 920–930

    Article  Google Scholar 

  • Williams PM (2003) Analytical descriptions of dynamic force spectroscopy: behaviour of multiple connections. Anal Chim Acta 479: 107–115

    Article  Google Scholar 

  • Yago T, Zarnitsyna VI, Klopocki AG, McEver RP, Zhu C (2007) Transport governs flow-enhanced cell tethering through L-selectin at threhold shear. Biophys J 92: 330–342

    Article  Google Scholar 

  • Zhang X, Bogorin DF, Moy VT (2004) Molecular basis of the dynamic strength of the sialyl Lewis X-selectin interaction. Chemphyschem 5: 175–182

    Article  Google Scholar 

  • Zhao Y, Chien S, Weinbaum S (2001) Dynamic contact forces on leukocyte microvilli and their penetration of the endothelial glycocalyx. Biophys J 80: 1124–1140

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Mechanical Engineering, University of Maryland, Baltimore County, Baltimore, MD, 21250, USA

    V. K. Gupta, Ihab A. Sraj & Charles D. Eggleton

  2. Department of Chemical and Biomolecular Engineering, The John Hopkins University, Baltimore, MD, 21218, USA

    Konstantinos Konstantopoulos

Authors
  1. V. K. Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ihab A. Sraj
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Konstantinos Konstantopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Charles D. Eggleton
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Charles D. Eggleton.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gupta, V.K., Sraj, I.A., Konstantopoulos, K. et al. Multi-scale simulation of L-selectin–PSGL-1-dependent homotypic leukocyte binding and rupture. Biomech Model Mechanobiol 9, 613–627 (2010). https://doi.org/10.1007/s10237-010-0201-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10237-010-0201-2

Keywords

Search

Navigation