Skip to main content

Journal for Biophysical Chemistry

Biointerphases Cover Image

Peptide-presenting two-dimensional protein matrix on supported lipid bilayers: An efficient platform for cell adhesion


Understanding and controlling cell adhesion to biomaterials and synthetic materials are important issues in basic research and applied sciences. Supported lipid bilayers (SLBs) functionalized with cell adhesion peptides linked to lipid molecules are popular platforms of cell adhesion. In this paper, an alternative approach of peptide presentation is presented in which peptides are stereo-selectively linked to proteins self-assembling in a rigid two-dimensional (2D) matrix on SLBs. Annexin-A5 (Anx5) was used as prototype protein for its known properties of forming stable and rigid 2D matrices on lipid surfaces. Two types of Anx5-peptide complexes, containing either a RGD or an IKVAV sequence, were synthesized. The authors show that both Anx5-peptide complexes present the same properties of binding and 2D organization on lipid surfaces as Anx5, when investigated by quartz crystal microbalance with dissipation monitoring, atomic force microscopy, and transmission electron microscopy techniques. Anx5-RGD and Anx5-IKVAV 2D matrices were found to promote specific adhesion of human saphenous vein endothelial cells and mouse embryonic stem cells, respectively. The influence of the surface density of exposed peptides on cell adhesion was investigated, showing that cells attach to Anx5-peptide matrices when the average distance between peptides is smaller than about 60 nm. This cell adhesion platform provides control of the orientation and density of cell ligands, opening interesting possibilities for future applications.


  1. 1

    A. Kikuchi and T. Okano, J. Control. Release 101, 69 (2005).

    CAS  Article  Google Scholar 

  2. 2

    A. K. Dillow and M. Tirrell, Curr. Opin. Solid State Mater. Sci. 3, 252 (1998).

    CAS  Article  Google Scholar 

  3. 3

    J. A. Hubbell, Curr. Opin. Biotechnol. 10, 123 (1999).

    CAS  Article  Google Scholar 

  4. 4

    M. Tanaka and E. Sackman, Nature (London) 437, 656 (2005).

    CAS  Article  Google Scholar 

  5. 5

    M. Tirrell, E. Kokkoli, and M. Biesalski, Surf. Sci. 500, 61 (2002).

    CAS  Article  Google Scholar 

  6. 6

    E. Ruoslahti, Annu. Rev. Cell Dev. Biol. 12, 697 (1996).

    CAS  Article  Google Scholar 

  7. 7

    U. Hersel, D. Claudia, and K. Horst, Biomaterials 24, 4385 (2003).

    CAS  Article  Google Scholar 

  8. 8

    S. Miyamoto, S. K. Akiyama, and K. M. Yamada, Science 267, 883 (1995).

    CAS  Article  Google Scholar 

  9. 9

    N. Q. Balaban, U. S. Schwarz, D. Riveline, P. Goichberg, G. Tzur, I. Sabanay, D. Mahalu, S. Safran, A. Bershadsky, L. Addadi, and B. Geiger, Nat. Cell Biol. 3, 466 (2001).

    CAS  Article  Google Scholar 

  10. 10

    M. Schuler, G. Owen, D. Hamilton, M. de Wild, M. Textor, D. M. Brunette, and S. Tosatti, Biomaterials 27, 4003 (2006).

    CAS  Article  Google Scholar 

  11. 11

    B. T. Houseman, E. S. Gawalt, and M. Mrksich, Langmuir 19, 1522 (2003).

    CAS  Article  Google Scholar 

  12. 12

    J. T. Groves and M. L. Dustin, J. Immunol. Methods 278, 19 (2003).

    CAS  Article  Google Scholar 

  13. 13

    E. Sackmann, Science 271, 43 (1996).

    CAS  Article  Google Scholar 

  14. 14

    R. P. Richter, R. Berat, and A. R. Brisson, Langmuir 22, 3497 (2006).

    CAS  Article  Google Scholar 

  15. 15

    A.-S. Andersson, K. Glasmästar, D. Sutherland, U. Lidberg, and B. Kasemo, J. Biomed. Mater. Res. 64A, 622 (2003).

    CAS  Article  Google Scholar 

  16. 16

    L. Kam and S. G. Boxer, J. Biomed. Mater. Res. 55, 487 (2001).

    CAS  Article  Google Scholar 

  17. 17

    L. Ruiz, E. Fine, J. Vörös, S. Makohliso, D. Léonard, D. Johnston, M. Textor, and H. Mathieu, J. Biomater. Sci. Polym. Ed. 10, 931 (1999).

    CAS  Article  Google Scholar 

  18. 18

    Y. Dori, H. Bianco-Peled, S. Satija, G. Fields, J. McCarthy, and M. Tirrell, J. Biomed. Mater. Res. 50, 75 (2000).

    CAS  Article  Google Scholar 

  19. 19

    M. Biesalski, A. Knaebel, R. Tu, and M. Tirrell, Biomaterials 27, 1259 (2006).

    CAS  Article  Google Scholar 

  20. 20

    T. Jensen, B. Hu, S. Delatore, A. Garcia, P. Messersmith, and W. Miller, J. Am. Chem. Soc. 126, 15223 (2004).

    CAS  Article  Google Scholar 

  21. 21

    R. V. Marchi-Artzne, B. Lorz, U. Hellerer, M. Kantlehner, H. Kessler, and E. Sackmann, Chemistry (Easton) 7, 1095 (2001).

    Google Scholar 

  22. 22

    S. E. Ochsenhirt, E. Kokkoli, J. B. McCarthy, and M. Tirrell, Biomaterials 27, 3863 (2006).

    CAS  Article  Google Scholar 

  23. 23

    T. Pakalns, K. L. Haverstick, G. B. Fields, J. B. McCarthy, D. L. Mooradian, and M. Tirrell, Biomaterials 20, 2265 (1999).

    CAS  Article  Google Scholar 

  24. 24

    S. Svedhem, D. Dahlborg, J. Ekeroth, J. Kelly, F. Hook, and J. Gold, Langmuir 19, 6730 (2003).

    CAS  Article  Google Scholar 

  25. 25

    D. Thid, K. Holm, P. S. Eriksson, J. Ekeroth, B. Kasemo, and J. Gold, J. Biomed. Mater. Res. A (2007).

  26. 26

    D. Stroumpoulis, H. Zhang, L. Rubalcava, J. Gliem, and M. Tirrell, Langmuir 23, 3849 (2007).

    CAS  Article  Google Scholar 

  27. 27

    D. Thid, Ph.D. thesis, Chalmers University of Technology, 2007.

  28. 28

    E. Uzgiris and R. Kornberg, Nature (London) 301, 125 (1983).

    CAS  Article  Google Scholar 

  29. 29

    A. Brisson, W. Bergsma-Schutter, F. Oling, O. Lambert, and I. Reviakine, J. Cryst. Growth 196, 456 (1999).

    CAS  Article  Google Scholar 

  30. 30

    I. Reviakine, W. Bergsma-Schutter, and A. Brisson, J. Struct. Biol. 121, 356 (1998).

    CAS  Article  Google Scholar 

  31. 31

    G. Mosser, C. Ravanat, J.-M. Freyssinet, and A. Brisson, J. Mol. Biol. 217, 241 (1991).

    CAS  Article  Google Scholar 

  32. 32

    D. Voges, R. Berendes, A. Burger, P. Demange, W. Baumeister, and R. Huber, J. Mol. Biol. 238, 199 (1994).

    CAS  Article  Google Scholar 

  33. 33

    F. Oling, W. Bergsma-Schutter, and A. Brisson, J. Struct. Biol. 133, 55 (2001).

    CAS  Article  Google Scholar 

  34. 34

    R. P. Richter and A. Brisson, Langmuir 19, 1632 (2003).

    CAS  Article  Google Scholar 

  35. 35

    R. P. Richter, J. Lai Kee Him, B. Tessier, C. Tessier, and A. R. Brisson, Biophys. J. 89, 3372 (2005).

    CAS  Article  Google Scholar 

  36. 36

    N. Govorukhina, W. Bergsma-Schutter, C. Mazeres-Dubut, S. Mazeres, E. Drakopoulou, L. Bystrykh, F. Oling, A. Mukhopadhyay, I. Reviakine, J. Lai Kee Him, and A. Brisson, in Annexins: Biological Importance and Annexin-related Pathologies, edited by J. Bandorowicz-Pikula (Landes Bioscience, Austin, TX, 2003), p. 61.

    Google Scholar 

  37. 37

    R. P. Richter, Ph.D. thesis, University Bordeaux 1, 2004.

  38. 38

    K. Tashiro, G. Sephel, B. Weeks, M. Sasaki, G. Martin, H. Kleinman, and Y. Yamada, J. Biol. Chem. 264, 16174 (1989).

    CAS  Google Scholar 

  39. 39

    N. Patel, R. Padera, G. Sanders, S. Cannizzaro, M. Davies, R. Langer, C. Roberts, S. Tendler, P. Williams, and K. Shakesheff, FASEB J. 12, 1447 (1998).

    CAS  Google Scholar 

  40. 40

    M. Sasaki, H. Kleinman, H. Huber, R. Deutzmann, and Y. Yamada, J. Biol. Chem. 263, 16536 (1988).

    CAS  Google Scholar 

  41. 41

    A. Nagy, J. Rossant, R. Nagy, W. Abramow-Newerly, and J. C. Roder, Proc. Natl. Acad. Sci. U.S.A. 90, 424 (1993).

    Google Scholar 

  42. 42

    R. Pepinsky, R. Tizard, R. Mattaliano, L. Sinclair, G. Miller, J. Browning, E. Chow, C. Burne, K. Huang, and D. Pratt, J. Biol. Chem. 263, 10799 (1988).

    CAS  Google Scholar 

  43. 43

    J. P. Schanstra, R. Rink, F. Pries, and D. B. Janssen, Protein Expr. Purif. 4, 479 (1993).

    CAS  Article  Google Scholar 

  44. 44

    G. Barany and R. B. Merrifield, in The Peptides: Analysis, Synthesis, Biology, edited by E. Gross and J. Meienhofer (Academic, New York, 1979), p. 1.

    Google Scholar 

  45. 45

    C. A. Keller and B. Kasemo, Biophys. J. 75, 1397 (1998).

    CAS  Article  Google Scholar 

  46. 46

    P. Fernandez, A. Deguette, L. Pothuaud, G. Belleannée, P. Coste, and L. Bordenave, Biomaterials 26, 5042 (2005).

    CAS  Article  Google Scholar 

  47. 47

    J. Golledge, R. J. Turner, S. L. Harley, and J. T. Powell, Eur. J. Vasc. Endovasc. Surg. 13, 605 (1997).

    CAS  Article  Google Scholar 

  48. 48

    J. Amedee, R. Bareille, R. Jeandot, L. Bordenave, M. Remy, F. Rouais, and C. Baquey, Biomaterials 15, 1029 (1994).

    CAS  Article  Google Scholar 

  49. 49

    S. Verrier, S. Pallu, R. Bareille, A. Jonczyk, J. Meyer, M. Dard, and J. Amédée, Biomaterials 23, 585 (2002).

    CAS  Article  Google Scholar 

  50. 50

    U. Landegren, J. Immunol. Methods 67, 379 (1984).

    CAS  Article  Google Scholar 

  51. 51

    M. Rodahl, F. Höök, A. Krozer, P. Brzezinski, and B. Kasemo, Rev. Sci. Instrum. 66, 3924 (1995).

    CAS  Article  Google Scholar 

  52. 52

    G. Sauerbrey, Z. Phys. A: Hadrons Nucl. 155, 206 (1959).

    CAS  Google Scholar 

  53. 53

    G. T. Oostergetel, W. Keegstra, and A. Brisson, J. Mol. Biol. 314, 245 (2001).

    CAS  Article  Google Scholar 

  54. 54

    R. Huber, J. Römisch, and E.-P. Paques, EMBO J. 9, 3867 (1990).

    CAS  Google Scholar 

  55. 55

    I. Reviakine, W. Bergsma-Schutter, C. Mazeres-Dubut, N. Govorukhina, and A. Brisson, J. Struct. Biol. 131, 234 (2000).

    CAS  Article  Google Scholar 

  56. 56

    B. Jarrell, E. Levine, S. Shapiro, S. Williams, R. A. Carabasi, S. Mueller, and S. Thornton, J. Vasc. Surg. 1, 757 (1984).

    CAS  Google Scholar 

  57. 57

    I. A. M. Relou, C. A. Damen, D. W. J. van der Schaft, G. Groenewegen, and A. W. Griffioen, Tissue Cell 30, 525 (1998).

    CAS  Article  Google Scholar 

  58. 58

    M. Arnold, E. A. Cavalcanti-Adam, R. Glass, J. Blümmel, W. Eck, M. Kantlehner, H. Kessler, and J. P. Spatz, Chem Phys Chem 5, 383 (2004).

    CAS  Article  Google Scholar 

  59. 59

    A. Janshoff and C. Steinem, Anal. Bioanal. Chem. 385, 433 (2006).

    CAS  Article  Google Scholar 

  60. 60

    R. Richter, A. Mukhopadhyay, and A. Brisson, Biophys. J. 85, 3035 (2003).

    CAS  Article  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Alain R. Brisson.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Bérat, R., Rémy-Zolghadry, M., Gounou, C. et al. Peptide-presenting two-dimensional protein matrix on supported lipid bilayers: An efficient platform for cell adhesion. Biointerphases 2, 165–172 (2007).

Download citation