Abstract
We present a theoretical and experimental analysis of the effects of nonlinear flow in a cone-plate viscometer. The analysis predicts that flow in the viscometer is a function of two parameters, the Reynolds number and the cone angle. Nonlinear flow occurs at high shear rates and causes spatial variations in wall shear stress, collision frequency, interparticle forces and attachment times within the viscometer. We examined the effect of these features on cellular adhesion kinetics. Based on recent data (Taylor, A. D., S. Neelamegham, J. D. Hellums, et al. 1996. Biophys. J. 71:3488-3500), we modeled neutrophil homotypic aggregation as a process that is integrin-limited at low shear and selectin-limited at high shear. Our calculations suggest that selectin and integrin on-rates lie in the order of 10(-2)-10(-4)/s. They also indicate that secondary flow causes positional variations in adhesion efficiency in the viscometer, and that the overall efficiency is dependent not only on the shear rate, but also the sample volume and the cone angle. Experiments performed with isolated neutrophils confirmed these predictions. In these experiments, enhancing secondary flow by increasing the sample volume from 100 to 1000 microl at 1500/s for a 2 degrees cone caused up to an approximately 45% drop in adhesion efficiency. Our results suggest that secondary flow may significantly influence cellular aggregation, platelet activation, and endothelial cell mechanotransduction measurements made in the viscometer over the range of conditions applied in typical biological studies.
Full Text
The Full Text of this article is available as a PDF (564.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bell G. I. Models for the specific adhesion of cells to cells. Science. 1978 May 12;200(4342):618–627. doi: 10.1126/science.347575. [DOI] [PubMed] [Google Scholar]
- Chang K. C., Hammer D. A. The forward rate of binding of surface-tethered reactants: effect of relative motion between two surfaces. Biophys J. 1999 Mar;76(3):1280–1292. doi: 10.1016/S0006-3495(99)77291-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen S., Springer T. A. An automatic braking system that stabilizes leukocyte rolling by an increase in selectin bond number with shear. J Cell Biol. 1999 Jan 11;144(1):185–200. doi: 10.1083/jcb.144.1.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dewey C. F., Jr Effects of fluid flow on living vascular cells. J Biomech Eng. 1984 Feb;106(1):31–35. doi: 10.1115/1.3138453. [DOI] [PubMed] [Google Scholar]
- Evans C. W., Proctor J. A collision analysis of lymphoid cell aggregation. J Cell Sci. 1978 Oct;33:17–36. doi: 10.1242/jcs.33.1.17. [DOI] [PubMed] [Google Scholar]
- Evans E., Ritchie K. Dynamic strength of molecular adhesion bonds. Biophys J. 1997 Apr;72(4):1541–1555. doi: 10.1016/S0006-3495(97)78802-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Finger E. B., Puri K. D., Alon R., Lawrence M. B., von Andrian U. H., Springer T. A. Adhesion through L-selectin requires a threshold hydrodynamic shear. Nature. 1996 Jan 18;379(6562):266–269. doi: 10.1038/379266a0. [DOI] [PubMed] [Google Scholar]
- Frangos J. A., Eskin S. G., McIntire L. V., Ives C. L. Flow effects on prostacyclin production by cultured human endothelial cells. Science. 1985 Mar 22;227(4693):1477–1479. doi: 10.1126/science.3883488. [DOI] [PubMed] [Google Scholar]
- Goto S., Ikeda Y., Saldívar E., Ruggeri Z. M. Distinct mechanisms of platelet aggregation as a consequence of different shearing flow conditions. J Clin Invest. 1998 Jan 15;101(2):479–486. doi: 10.1172/JCI973. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Guyer D. A., Moore K. L., Lynam E. B., Schammel C. M., Rogelj S., McEver R. P., Sklar L. A. P-selectin glycoprotein ligand-1 (PSGL-1) is a ligand for L-selectin in neutrophil aggregation. Blood. 1996 Oct 1;88(7):2415–2421. [PubMed] [Google Scholar]
- Haidekker M. A., L'Heureux N., Frangos J. A. Fluid shear stress increases membrane fluidity in endothelial cells: a study with DCVJ fluorescence. Am J Physiol Heart Circ Physiol. 2000 Apr;278(4):H1401–H1406. doi: 10.1152/ajpheart.2000.278.4.H1401. [DOI] [PubMed] [Google Scholar]
- Hammer D. A., Lauffenburger D. A. A dynamical model for receptor-mediated cell adhesion to surfaces. Biophys J. 1987 Sep;52(3):475–487. doi: 10.1016/S0006-3495(87)83236-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hentzen E. R., Neelamegham S., Kansas G. S., Benanti J. A., McIntire L. V., Smith C. W., Simon S. I. Sequential binding of CD11a/CD18 and CD11b/CD18 defines neutrophil capture and stable adhesion to intercellular adhesion molecule-1. Blood. 2000 Feb 1;95(3):911–920. [PubMed] [Google Scholar]
- Holme P. A., Orvim U., Hamers M. J., Solum N. O., Brosstad F. R., Barstad R. M., Sakariassen K. S. Shear-induced platelet activation and platelet microparticle formation at blood flow conditions as in arteries with a severe stenosis. Arterioscler Thromb Vasc Biol. 1997 Apr;17(4):646–653. doi: 10.1161/01.atv.17.4.646. [DOI] [PubMed] [Google Scholar]
- Ikeda Y., Handa M., Kawano K., Kamata T., Murata M., Araki Y., Anbo H., Kawai Y., Watanabe K., Itagaki I. The role of von Willebrand factor and fibrinogen in platelet aggregation under varying shear stress. J Clin Invest. 1991 Apr;87(4):1234–1240. doi: 10.1172/JCI115124. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jen C. J., McIntire L. V. Characteristics of shear-induced aggregation in whole blood. J Lab Clin Med. 1984 Jan;103(1):115–124. [PubMed] [Google Scholar]
- Kishimoto T. K., Jutila M. A., Berg E. L., Butcher E. C. Neutrophil Mac-1 and MEL-14 adhesion proteins inversely regulated by chemotactic factors. Science. 1989 Sep 15;245(4923):1238–1241. doi: 10.1126/science.2551036. [DOI] [PubMed] [Google Scholar]
- Kroll M. H., Hellums J. D., McIntire L. V., Schafer A. I., Moake J. L. Platelets and shear stress. Blood. 1996 Sep 1;88(5):1525–1541. [PubMed] [Google Scholar]
- Kuchan M. J., Frangos J. A. Role of calcium and calmodulin in flow-induced nitric oxide production in endothelial cells. Am J Physiol. 1994 Mar;266(3 Pt 1):C628–C636. doi: 10.1152/ajpcell.1994.266.3.C628. [DOI] [PubMed] [Google Scholar]
- Lawrence M. B., Kansas G. S., Kunkel E. J., Ley K. Threshold levels of fluid shear promote leukocyte adhesion through selectins (CD62L,P,E) J Cell Biol. 1997 Feb 10;136(3):717–727. doi: 10.1083/jcb.136.3.717. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Merkel R., Nassoy P., Leung A., Ritchie K., Evans E. Energy landscapes of receptor-ligand bonds explored with dynamic force spectroscopy. Nature. 1999 Jan 7;397(6714):50–53. doi: 10.1038/16219. [DOI] [PubMed] [Google Scholar]
- Moake J. L., Turner N. A., Stathopoulos N. A., Nolasco L., Hellums J. D. Shear-induced platelet aggregation can be mediated by vWF released from platelets, as well as by exogenous large or unusually large vWF multimers, requires adenosine diphosphate, and is resistant to aspirin. Blood. 1988 May;71(5):1366–1374. [PubMed] [Google Scholar]
- Neelamegham S., Taylor A. D., Burns A. R., Smith C. W., Simon S. I. Hydrodynamic shear shows distinct roles for LFA-1 and Mac-1 in neutrophil adhesion to intercellular adhesion molecule-1. Blood. 1998 Sep 1;92(5):1626–1638. [PubMed] [Google Scholar]
- Neelamegham S., Taylor A. D., Hellums J. D., Dembo M., Smith C. W., Simon S. I. Modeling the reversible kinetics of neutrophil aggregation under hydrodynamic shear. Biophys J. 1997 Apr;72(4):1527–1540. doi: 10.1016/S0006-3495(97)78801-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Neelamegham S., Taylor A. D., Shankaran H., Smith C. W., Simon S. I. Shear and time-dependent changes in Mac-1, LFA-1, and ICAM-3 binding regulate neutrophil homotypic adhesion. J Immunol. 2000 Apr 1;164(7):3798–3805. doi: 10.4049/jimmunol.164.7.3798. [DOI] [PubMed] [Google Scholar]
- Ohno M., Gibbons G. H., Dzau V. J., Cooke J. P. Shear stress elevates endothelial cGMP. Role of a potassium channel and G protein coupling. Circulation. 1993 Jul;88(1):193–197. doi: 10.1161/01.cir.88.1.193. [DOI] [PubMed] [Google Scholar]
- Peterson D. M., Stathopoulos N. A., Giorgio T. D., Hellums J. D., Moake J. L. Shear-induced platelet aggregation requires von Willebrand factor and platelet membrane glycoproteins Ib and IIb-IIIa. Blood. 1987 Feb;69(2):625–628. [PubMed] [Google Scholar]
- Puri K. D., Chen S., Springer T. A. Modifying the mechanical property and shear threshold of L-selectin adhesion independently of equilibrium properties. Nature. 1998 Apr 30;392(6679):930–933. doi: 10.1038/31954. [DOI] [PubMed] [Google Scholar]
- Schmidtke D. W., Diamond S. L. Direct observation of membrane tethers formed during neutrophil attachment to platelets or P-selectin under physiological flow. J Cell Biol. 2000 May 1;149(3):719–730. doi: 10.1083/jcb.149.3.719. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shao J. Y., Ting-Beall H. P., Hochmuth R. M. Static and dynamic lengths of neutrophil microvilli. Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6797–6802. doi: 10.1073/pnas.95.12.6797. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Simon S. I., Chambers J. D., Butcher E., Sklar L. A. Neutrophil aggregation is beta 2-integrin- and L-selectin-dependent in blood and isolated cells. J Immunol. 1992 Oct 15;149(8):2765–2771. [PubMed] [Google Scholar]
- Springer T. A. Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration. Annu Rev Physiol. 1995;57:827–872. doi: 10.1146/annurev.ph.57.030195.004143. [DOI] [PubMed] [Google Scholar]
- Tandon P., Diamond S. L. Kinetics of beta2-integrin and L-selectin bonding during neutrophil aggregation in shear flow. Biophys J. 1998 Dec;75(6):3163–3178. doi: 10.1016/S0006-3495(98)77758-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Taylor A. D., Neelamegham S., Hellums J. D., Smith C. W., Simon S. I. Molecular dynamics of the transition from L-selectin- to beta 2-integrin-dependent neutrophil adhesion under defined hydrodynamic shear. Biophys J. 1996 Dec;71(6):3488–3500. doi: 10.1016/S0006-3495(96)79544-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tha S. P., Goldsmith H. L. Interaction forces between red cells agglutinated by antibody. I. Theoretical. Biophys J. 1986 Dec;50(6):1109–1116. doi: 10.1016/S0006-3495(86)83555-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tha S. P., Shuster J., Goldsmith H. L. Interaction forces between red cells agglutinated by antibody. II. Measurement of hydrodynamic force of breakup. Biophys J. 1986 Dec;50(6):1117–1126. doi: 10.1016/S0006-3495(86)83556-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tsao P. S., Buitrago R., Chan J. R., Cooke J. P. Fluid flow inhibits endothelial adhesiveness. Nitric oxide and transcriptional regulation of VCAM-1. Circulation. 1996 Oct 1;94(7):1682–1689. doi: 10.1161/01.cir.94.7.1682. [DOI] [PubMed] [Google Scholar]
- Wagner C. T., Durante W., Christodoulides N., Hellums J. D., Schafer A. I. Hemodynamic forces induce the expression of heme oxygenase in cultured vascular smooth muscle cells. J Clin Invest. 1997 Aug 1;100(3):589–596. doi: 10.1172/JCI119569. [DOI] [PMC free article] [PubMed] [Google Scholar]