Journal of Bionic Engineering

, Volume 5, Issue 4, pp 317–327 | Cite as

Biomimetic Leukocyte Adhesion: A Review of Microfluidic and Computational Approaches and Applications

  • J. Hanzlik
  • E. Cretekos
  • K. A. Lamkin-KennardEmail author


Leukocyte rolling and adhesion are complex physiological processes that have received a great deal of attention over the past decade. Significant increases in the knowledge base related to how leukocytes adhere in shear flows have occurred as a result of the development of novel experimental and computational techniques. Micro- and nano-fabrication techniques have enabled the development of novel flow devices for studying leukocyte adhesion in simple and complex geometries. Improvements in computer technology have enabled simulations of complex flow processes to be developed. As a result of these advances in knowledge related to leukocyte adhesion, numerous novel devices have been developed that mimic the leukocyte rolling and adhesion process. Examples of these devices include cell separation and enrichment devices and targeted ultrasound contrast agents. Future advances related to leukocyte rolling and adhesion processes hold great promise for advancing our knowledge of disease processes as well as development of novel therapeutic devices.


leukocyte microfluidics hydrodynamics 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. [1]
    Bhatia S K, King M R, Hammer D A. The state diagram for cell adhesion mediated by two receptors. Biophysical Journal, 2003, 84, 2671–2690.CrossRefGoogle Scholar
  2. [2]
    Lev K. Physiology of Inflammation, Oxford Press, New York, 2001.Google Scholar
  3. [3]
    King M R, Hammer D A. Multiparticle adhesive dynamics. Interactions between stably rolling cells. Biophysical Journal, 2001, 81, 799–813.CrossRefGoogle Scholar
  4. [4]
    King M R, Hammer D A. Multiparticle adhesive dynamics: Hydrodynamic recruitment of rolling leukocytes. Proceedings of the National Academy of Sciences, 2001, 98, 14919–14924.CrossRefGoogle Scholar
  5. [5]
    Prabhakarpandian B, Pant K, Scott R C, Patillo C B, Irimia D, Kiani M F, Sundaram S. Synthetic microvascular networks for quantitative analysis of particle adhesion. Biomedical microdevices, 2008, 10, 585–595.CrossRefGoogle Scholar
  6. [6]
    Munn L L, Melder R J, Jain R K. Role of erythrocytes in leukocyte-endothelial interactions: Mathematical model and experimental validation. Biophysical Journal, 1996, 71, 466–478.CrossRefGoogle Scholar
  7. [7]
    Koslow A R, Stromberg R R, Friedman L I, Lutz R J, Hilbert S L, Schuster P. A flow system for the study of shear forces upon cultured endothelial cells. Journal of Biomechanical Engineering, 1986, 108, 338–341.CrossRefGoogle Scholar
  8. [8]
    Viggers R F, Wechezak A R, Sauvage L R. An apparatus to study the response of cultured endothelium to shear stress. Journal of Biomechanical Engineering, 1986, 108, 332–337.CrossRefGoogle Scholar
  9. [9]
    Forrester J V, Lackie J M. Adhesion of neutrophil leucocytes under conditions of flow. Journal of Cell Science, 1984, 70, 93–110.Google Scholar
  10. [10]
    Koslow A R, Stromberg R R, Friedman L I, Lutz R J, Hilbert S L, Schuster P. A flow system for the study of shear forces upon cultured endothelial cells. Journal of Biomechanical Engineering, 1986, 108, 338–341.CrossRefGoogle Scholar
  11. [11]
    Eskin S G, Ives C L, McIntire L V, Navarro L T. Response of cultured endothelial cells to steady flow. Microvascular Research, 1984, 28, 87–94.CrossRefGoogle Scholar
  12. [12]
    Goetz D J, el-Sabban M E, Pauli B U, Hammer D A. Dynamics of neutrophil rolling over stimulated endothelium in vitro. Biophysical Journal, 1996, 66, 2202–2209.CrossRefGoogle Scholar
  13. [13]
    Burch E E, Shinde Patil V R, Camphausen R T, Kiani M F, Goetz D J. The N-terminal peptide of PSGL-1 can mediate adhesion to trauma-activated endothelium via P-selectin in vivo. Blood, 2002, 100, 531–538.CrossRefGoogle Scholar
  14. [14]
    Ruel J, Lemay J, Dumas G, Doillon C, Charara J. Development of a parallel plate flow chamber for studying cell behavior under pulsatile flow. ASAIO Journal, 1995, 41, 876–883.CrossRefGoogle Scholar
  15. [15]
    Otto M, Klein C L, Köhler H, Wagner M, Röhrig O, Kirkpatrick C J. Dynamic blood cell contact with biomaterials: validation of a flow chamber system according to international standards. Journal of Materials Science: Materials in Medicine, 1997, 8, 119–129.Google Scholar
  16. [16]
    Rainger G E, Stone P, Morland C M, Nash G B. A novel system for investigating the ability of smooth muscle cells and fibroblasts to regulate adhesion of flowing leukocytes to endothelial cells. Journal of Immunological Methods, 2001, 255, 73–82.CrossRefGoogle Scholar
  17. [17]
    Goldsmith H L, Turitto V T. Rheological aspects of thrombosis and haemostasis: basic principles and applications. ICTH-Report-Subcommittee on Rheology of the International Committee on Thrombosis and Haemostasis. Journal of Thrombosis and Haemostasis, 1986, 55, 415–435.Google Scholar
  18. [18]
    Lamkin-Kennard K A, Chuang J H, Kim M B, Sarelius I H, King M R. The distribution of rolling neutrophils in venular convergences. Biorheology, 2005, 42, 363–383.Google Scholar
  19. [19]
    Kim M B, Sarelius I H. Role of shear forces and adhesion molecules distribution on P-selectin-mediated leukocyte rolling in postcapillary venules. American Journal of Physiology: Heart and Circulatory, 2004, 287, 2705–2711.Google Scholar
  20. [20]
    Cokelet G R, Soave R, Pugh G, Rathbun L. Fabrication of in vitro microvascular blood flow systems by photolithography. Microvascular Research, 1993, 46, 394–400.CrossRefGoogle Scholar
  21. [21]
    Frame M D, Sarelius I H. A system for culture of endothelial cells in 20–50-microns branching tubes. Microcirculation, 1995, 2, 377–385.CrossRefGoogle Scholar
  22. [22]
    Lu H, Koo L Y, Wang W M, Lauffenburger D A, Griffith L G, Jensen K F. Microfluidic shear devices for quantitative analysis of cell adhesion. Analytical Chemistry, 2004, 76, 5257–5264.CrossRefGoogle Scholar
  23. [23]
    Martines E, McGhee K, Wilkinson C, Curtis A. A parallel-plate flow chamber to study initial cell adhesion on a nanofeatured surface. IEEE Transactions Nanobioscience, 2004, 3, 90–95.CrossRefGoogle Scholar
  24. [24]
    Sumagin R, Brown CW 3rd, Sarelius I H, King M R. Microvascular endothelial cells exhibit optimal aspect ratio for minimizing flow resistance. Annals of Biomedical Engineering, 2008, 36, 580–585.CrossRefGoogle Scholar
  25. [25]
    Chapman G B, Cokelet G R. Flow resistance and drag forces due to multiple adherent leukocytes in postcapillary vessels. Biophysical Journal, 1998, 74, 3292–3301.CrossRefGoogle Scholar
  26. [26]
    Bagchi P, Johnson P C, Popel A S. Computational fluid dynamic simulation of aggregation of deformable cells in a shear flow. Journal of Biomechanical Engineering, 2005, 127, 1070–1080.CrossRefGoogle Scholar
  27. [27]
    Skilbeck C A, Walker P G, David T, Nash G B. Disturbed flow promotes deposition of leucocytes from flowing whole blood in a model of a damaged vessel wall. British Journal of Haematology, 2004, 126, 418–427.CrossRefGoogle Scholar
  28. [28]
    Chapman G B, Cokelet G R. Model studies of leukocyte-endothelium-blood interactions. II. Hemodynamic impact of leukocytes adherent to the wall of post-capillary vessels. Biorheology, 1997, 34, 37–56.Google Scholar
  29. [29]
    Migliorini C, Qian Y, Chen H, Brown E B, Jain R K, Munn L L. Red blood cells augment leukocyte rolling in a virtual blood vessel. Biophysical Journal, 2002, 83, 1834–1841.CrossRefGoogle Scholar
  30. [30]
    Jadhav S, Eggleton C D, Konstantopoulos K. A 3-D computational model predicts that cell deformation affects selectin-mediated leukocyte rolling. Biophysical Journal, 2005, 88, 96–104.CrossRefGoogle Scholar
  31. [31]
    Hammer D A, Apte S M. Simulation of cell rolling and adhesion on surfaces in shear flow: General results and analysis of selectin-mediated neutrophil adhesion. Biophysical Journal, 1992, 62, 35–57.CrossRefGoogle Scholar
  32. [32]
    Bell G I, Dembo M, Bongrand P. Competition between non-specific repulsion and specific bonding. Biophysical Journal, 1984, 45, 1051–1064.CrossRefGoogle Scholar
  33. [33]
    Dembo M., Torney D C, Saxman K, Hammer D A. The reaction-limited kinetics of membrane-to-surface adhesion and detachment. Proceedings of the Royal Society of London B, 1988, 234, 55–83.CrossRefGoogle Scholar
  34. [34]
    Caputo K E, Lee D, King M R, Hammer D A. Adhesive dynamics simulations of the shear threshold effect for leukocytes. Biophysical Journal, 2007, 92, 787–797.CrossRefGoogle Scholar
  35. [35]
    Sun C, Migliorini C, Munn L L. Red blood cells initiate leukocyte rolling in postcapillary expansions: A lattice Boltzmann analysis. Biophysical Journal, 2003, 85, 208–222.CrossRefGoogle Scholar
  36. [36]
    Sun C, Munn L L. Particulate nature of blood determines macroscopic rheology: A 2D lattice Boltzmann analysis. Biophysical Journal, 2005, 88, 1635–1645.CrossRefGoogle Scholar
  37. [37]
    Goldsmith H L, Karino T. Interactions of human blood cells with the vascular endothelium. Annals of the New York Academy of Sciences, 1987, 516, 468–483.CrossRefGoogle Scholar
  38. [38]
    Charles N, Liesveld J L, King M R. Investigating the feasibility of stem cell enrichment mediated by immobilized selectins. Biotechnology Progress, 2007, 23, 1463–1472.CrossRefGoogle Scholar
  39. [39]
    Revzin A, Sekine K, Sin A, Tompkins R G, Toner M. Development of a microfabricated cytometry platform for characterization and sorting of individual leukocytes. Lab on a Chip, 2005, 5, 30–37.CrossRefGoogle Scholar
  40. [40]
    Greenberg A W, Hammer D A. Cell separation mediated by differential rolling adhesion. Biotechnology and Bioengineering, 2001, 73, 111–124.CrossRefGoogle Scholar
  41. [41]
    Narasipura S D, Wojciechowski J C, Charles N, Liesveld J L, King M R. P-Selectin coated microtube for enrichment of CD34+ hematopoietic stem and progenitor cells from human bone marrow. Clinical Chemistry, 2008, 54, 77–85.CrossRefGoogle Scholar
  42. [42]
    Behm C Z, Lindner J R. Cellular and molecular imaging with targeted contrast ultrasound. Ultrasound Quarterly, 2006, 22, 67–72.Google Scholar
  43. [43]
    Klibanov A L Microbubble contrast agents: Targeted ultrasound imaging and ultrasound-assisted drug-delivery applications. Investigative Radiology, 2006, 41, 354–362.CrossRefGoogle Scholar
  44. [44]
    Plouffe B D, Radisic M, Murthy S K. Microfluidic depletion of endothelial cells, smooth muscle cells, and fibroblasts from heterogeneous suspensions. Lab on a Chip, 2007, 8, 462–472.CrossRefGoogle Scholar
  45. [45]
    Wojciechowski J C, Narasipura S D, Charles N, Mickelsen D, Rana K, Blair M L, King M R. Capture and enrichment of CD34-positive haematopoietic stem and progenitor cells from blood circulation using P-selectin in an implantable device. British Journal of Haematology, 2008, 140, 673–681.CrossRefGoogle Scholar
  46. [46]
    Kwon K W, Choi S S, Lee S H, Kim B, Lee S N, Park M C, Kim P, Hwang S Y, Suh K Y. Label-free, microfluidic separation and enrichment of human breast cancer cells by adhesion difference. Lab on a Chip, 2007, 7, 1461–1468.CrossRefGoogle Scholar

Copyright information

© Jilin University 2008

Authors and Affiliations

  • J. Hanzlik
    • 1
  • E. Cretekos
    • 1
  • K. A. Lamkin-Kennard
    • 1
    Email author
  1. 1.Department of Mechanical EngineeringRochester Institute of TechnologyRochesterUSA

Personalised recommendations