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Protein resistant surfaces: Comparison of acrylate graft polymers bearing oligo-ethylene oxide and phosphorylcholine side chains


The objective of this work was to compare poly(ethylene glycol) (PEG) and phosphorylcholine (PC) moieties as surface modifiers with respect to their ability to inhibit protein adsorption. Surfaces were prepared by graft polymerization of the methacrylate monomers oligo(ethylene glycol) methyl ether methacrylate (OEGMA, MW 300, PEG side chains of length n=4.5) and 2-methacryloyloxyethyl phosphorylcholine (MPC, MW295). The grafted polymers thus contained short PEG chains and PC, respectively, as side groups. Grafting on silicon was carried out using surface-initiated atom transfer radical polymerization (ATRP). Graft density was controlled via the surface density of the ATRP initiator, and chain length of the grafts was controlled via the ratio of monomer to sacrificial initiator. The grafted surfaces were characterized by water contact angle, x-ray photoelectron spectroscopy, and atomic force microscopy. The effect of graft density and chain length on fibrinogen adsorption from buffer was investigated using radio labeling methods. Adsorption to both MPC- and OEGMA-grafted surfaces was found to decrease with increasing graft density and chain length. Adsorption on the MPC and OEGMA surfaces for a given chain length and density was essentially the same. Very low adsorption levels of the order of 7 ng/cm2 were seen on the most resistant surfaces. The effect of protein size on resistance to adsorption was studied using binary solutions of lysozyme (MW 14 600) and fibrinogen (MW 340 000). Adsorption levels in these experiments were also greatly reduced on the grafted surfaces compared to the control surfaces. It was concluded that at the lowest graft density, both proteins had unrestricted access to the substrate, and the relative affinities of the proteins for the substrate (higher affinity of fibrinogen) determined the composition of the layer. At the highest graft density also, where the adsorption of both proteins was very low, no preference for one or the other protein was evident, suggesting that adsorption did not involve penetration of the grafts and was occurring at the outer surface of the graft layer. It thus seems likely that preference among different proteins based on ability to penetrate the graft layer would occur, if at all, at a grafting density intermediate between 0.1 and 0.39 /cm2. Again the MPC and OEGMA surfaces behaved similarly. It is suggested that the main determinant of the protein resistance of these surfaces is the “water barrier layer” resulting from their hydrophilic character. In turn the efficacy of the water barrier depends on the monomer density in the graft layer.


  1. 1

    Proteins at Interfaces II, Fundamentals and Applications, edited by T. A. Horbett and J. L. Brash, ACS Symposium Series No. 602 (American Chemical Society, Washington, DC, 1995).

  2. 2

    D. G. Castner and B. D. Ratner, Surf. Sci. 500, 28 (2002).

    Article  CAS  Google Scholar 

  3. 3

    J. L. Brash, J. Biomater. Sci., Polym. Ed. 11, 1135 (2000).

    Article  CAS  Google Scholar 

  4. 4

    B. D. Ratner and S. J. Bryant, Annu. Rev. Biomed. Eng. 6, 41 (2004).

    Article  CAS  Google Scholar 

  5. 5

    B. Kasemo, Surf. Sci. 500, 656 (2002).

    Article  CAS  Google Scholar 

  6. 6

    J. H. Lee and J. D. Andrade, Prog. Polym. Sci. 20, 1043 (1995).

    Article  CAS  Google Scholar 

  7. 7

    P. Vermette and L. Meagher, Colloids Surf., B 28, 153 (2003).

    Article  CAS  Google Scholar 

  8. 8

    H. J. Mathieu, Y. Chevolot, L. Ruiz-Taylor, and D. Leonard, Adv. Polym. Sci. 162, 1 (2003).

    Article  CAS  Google Scholar 

  9. 9

    Y. Iwasaki and K. Ishihara, Anal. Bioanal. Chem. 381, 534 (2005).

    Article  CAS  Google Scholar 

  10. 10

    S. I. Jeon, J. H. Lee, J. D. Andrade, and P. G. De Gennes, J. Colloid Interface Sci. 142, 149 (1991).

    Article  CAS  Google Scholar 

  11. 11

    I. Szleifer, Biophys. J. 72, 595 (1997).

    Article  CAS  Google Scholar 

  12. 12

    T. McPherson, A. Kidane, I. Szleifer, and K. Park, Langmuir 14, 176 (1998).

    Article  CAS  Google Scholar 

  13. 13

    M. Jonsson and H. O. Johansson, Colloids Surf., B 37, 71 (2004).

    Article  Google Scholar 

  14. 14

    W. Norde and D. Gage, Langmuir 20, 4162 (2004).

    Article  CAS  Google Scholar 

  15. 15

    L. D. Unsworth, H. Sheardown, and J. L. Brash, Langmuir d21, 1036 (2005).

    Article  Google Scholar 

  16. 16

    G. L. Kenausis, J. Voros, D. L. Elbert, N. Huang, R. Hofer, L. Ruiz-Taylor, M. Textor, J. A. Hubbell, and N. D. Spencer, J. Phys. Chem. B 104, 3298 (2000).

    Article  CAS  Google Scholar 

  17. 17

    J. G. Archambault and J. L. Brash, Colloids Surf., B 33, 111 (2004).

    Article  CAS  Google Scholar 

  18. 18

    K. L. Prime and G. M. Whitesides, Science 252, 1164 (1991).

    Article  CAS  Google Scholar 

  19. 19

    K. L. Prime and G. M. Whitesides, J. Am. Chem. Soc. 115, 10174 (1993).

    Article  Google Scholar 

  20. 20

    P. Harder, M. Grunze, R. Dahint, G. M. Whitesides, and P. E. Laibinis, J. Phys. Chem. B 102, 426 (1998).

    Article  CAS  Google Scholar 

  21. 21

    S. Herrwerth, W. Eck, S. Reinhardt, and M. Grunze, J. Am. Chem. Soc. 125, 9359 (2003).

    Article  CAS  Google Scholar 

  22. 22

    D. V. Vanderah, H. La, J. Naff, V. Silin, and K. A. Rubinson, J. Am. Chem. Soc. 126, 13639 (2004).

    Article  CAS  Google Scholar 

  23. 23

    J. H. Lee, J. Kopecek and J. D. Andrade, J. Biomed. Mater. Res. 23, 351 (1989).

    Article  Google Scholar 

  24. 24

    S. B. Jo and K. Park, Biomaterials 21, 605 (2000).

    Article  CAS  Google Scholar 

  25. 25

    S. J. Sofia, V. Premnath, and E. W. Merrill, Macromolecules 31, 5059 (1998).

    Article  CAS  Google Scholar 

  26. 26

    J. Groll, Z. Ademovic, T. Ameringer, D. Klee, and M. Moeller, Biomacromolecules 6, 956 (2005).

    Article  CAS  Google Scholar 

  27. 27

    J. Benesch, S. Svedhem, S. C. T. Svensson, R. Valiokas, B. Liedberg, and P. Tengvall, J. Biomater. Sci., Polym. Ed. 12, 581 (2001).

    Article  CAS  Google Scholar 

  28. 28

    Y. Mori, S. Nagaoka, H. Takiuchi, T. Kikuchi, N. Noguchi, H. Tanzawa, and Y. Noishiki, Trans. ASAIO 28, 459 (1982).

    CAS  Google Scholar 

  29. 29

    S. Nagaoka and A. Nakao, Biomaterials 11, 119 (1990).

    Article  CAS  Google Scholar 

  30. 30

    Y. H. Sun, A. S. Hoffman, and W. R. Gombotz, Polym. Prepr. (Am. Chem. Soc. Div. Polym. Chem.) 28, 292 (1987).

    CAS  Google Scholar 

  31. 31

    K. Fujimoto, H. Inoue, and Y. Ikada, J. Biomed. Mater. Res. 27, 1559 (1993).

    Article  CAS  Google Scholar 

  32. 32

    F. Zhang, E. T. Kang, K. G. Neoh, P. Wang, and K. L. Tan, J. Biomed. Mater. Res. 56, 324 (2001).

    Article  CAS  Google Scholar 

  33. 33

    W. Feng, R. X. Chen, J. L. Brash, and S. P. Zhu, Macromol. Rapid Commun. 26, 1383 (2005).

    Article  CAS  Google Scholar 

  34. 34

    F. J. Xu, Y. L. Li, E. T. Kang, and K. G. Neoh, Biomacromolecules 6, 1759 (2005).

    Article  CAS  Google Scholar 

  35. 35

    H. W. Ma, J. H. Hyun, P. Stiller, and A. Chilkoti, Adv. Mater. (Weinheim, Ger.) 16, 338 (2004).

    Article  CAS  Google Scholar 

  36. 36

    X. W. Fan, L. J. Lin, J. L. Dalsin, and P. B. Messersmith, J. Am. Chem. Soc. 127, 15843 (2005).

    Article  CAS  Google Scholar 

  37. 37

    A. L. Lewis, Colloids Surf., B 18, 261 (2000).

    Article  CAS  Google Scholar 

  38. 38

    V. A. Tegoulia, W. S. Rao, A. T. Kalambur, J. F. Rabolt, and S. L. Cooper, Langmuir 17, 4396 (2001).

    Article  CAS  Google Scholar 

  39. 39

    K. Ishihara, H. Nomura, T. Mihara, K. Kurita, Y. Iwasaki, and N. Nakabayashi, J. Biomed. Mater. Res. 39, 323 (1998).

    Article  CAS  Google Scholar 

  40. 40

    H. Kitano, K. Sudo, K. Ichikawa, M. Ide, and K. Ishihara, J. Phys. Chem. B 104, 11425 (2000).

    Article  CAS  Google Scholar 

  41. 41

    J. R. Lu, E. F. Murphy, T. J. Su, A. L. Lewis, P. W. Stratford, and S. K. Satija, Langmuir 17, 3382 (2001).

    Article  CAS  Google Scholar 

  42. 42

    E. Ostuni, R. G. Chapman, R. E. Holmlin, S. Takayama, and G. M. Whitesides, Langmuir 17, 5605 (2001).

    Article  CAS  Google Scholar 

  43. 43

    S. F. Chen, J. Zhang, L. Y. Li, and S. Y. Jiang, J. Am. Chem. Soc. 127, 14473 (2005).

    Article  CAS  Google Scholar 

  44. 44

    A. Korematsu, Y. Takemoto, T. Nakaya, and H. Inoue, Biomaterials 23, 263 (2002).

    Article  CAS  Google Scholar 

  45. 45

    K. Kim, C. Kim, and Y. Byun, Biomaterials 25, 33 (2004).

    Article  CAS  Google Scholar 

  46. 46

    T. Moro, Y. Takatori, K. Ishihara, T. Konno, Y. Takigawa, T. Matsushita, U. I. Chung, K. Nakamura, and H. Kawaguchi, Nat. Mater. 3, 829 (2004).

    Article  CAS  Google Scholar 

  47. 47

    X. Y. Chen and S. P. Armes, Adv. Mater. (Weinheim, Ger.) 15, 1558 (2003).

    Article  CAS  Google Scholar 

  48. 48

    R. Iwata, P. Suk-In, V. P. Hoven, A. Takahara, K. Akiyoshi, and Y. Iwasaki, Biomacromolecules 5, 2308 (2004).

    Article  CAS  Google Scholar 

  49. 49

    W. Feng, J. L. Brash, and S. P. Zhu, J. Polym. Sci., Part A: Polym. Chem. 42, 2931 (2004).

    Article  CAS  Google Scholar 

  50. 50

    W. Feng, J. L. Brash, and S. P. Zhu, Biomaterials 27, 847 (2006).

    Article  CAS  Google Scholar 

  51. 51

    W. Feng, S. P. Zhu, K. Ishihara, and J. L. Brash, Langmuir 21, 5980 (2005).

    Article  CAS  Google Scholar 

  52. 52

    K. Ishihara, T. Ueda, and N. Nakabayashi, Polym. J. (Tokyo, Jpn.) 22, 355 (1990).

    Article  CAS  Google Scholar 

  53. 53

    X. Jin, Y. Shen, and S. P. Zhu, Macromol. Mater. Eng. 288, 925 (2003).

    Article  CAS  Google Scholar 

  54. 54

    M. Husseman, E. E. Malmstrom, M. McNamara, M. Mate, D. Mecerreyes, D. G. Benoit, J. L. Hedrick, P. Mansky, E. Huang, T. P. Russell, and C. J. Hawker, Macromolecules 32, 1424 (1999).

    Article  CAS  Google Scholar 

  55. 55

    I. Y. Ma, E. J. Lobb, N. C. Billingham, S. P. Armes, A. L. Lewis, A. W. Lloyd, and J. Salvage, Macromolecules 35, 9306 (2002).

    Article  CAS  Google Scholar 

  56. 56

    Density of poly(OEGMA) measured in house.

  57. 57

    K. Yamamoto, Y. Miwa, H. Tanaka, M. Sakaguchi, and S. Shimada, J. Polym. Sci., Part A: Polym. Chem. 40, 3350 (2002).

    Article  CAS  Google Scholar 

  58. 58

    L. Andruzzi, W. Senaratne, A. Hexemer, E. D. Sheets, B. Ilic, E. J. Kramer, B. Baird, and C. K. Ober, Langmuir 21, 2495 (2005).

    Article  CAS  Google Scholar 

  59. 59

    T. Wu, K. Efimenko, and J. Genzer, J. Am. Chem. Soc. 124, 9394 (2002).

    Article  CAS  Google Scholar 

  60. 60

    J. Kim and G. A. Somorjai, J. Am. Chem. Soc. 12, 3150 (2003).

    Article  Google Scholar 

  61. 61

    A. Halperin, Langmuir 15, 2525 (1999).

    Article  CAS  Google Scholar 

  62. 62

    S. Pasche, M. Textor, L. Meagher, N. D. Spencer, and H. J. Griesser, Langmuir 21, 6508 (2005).

    Article  CAS  Google Scholar 

  63. 63

    J. Zhang, L. Y. Li, H. K. Tsao, Y. J. Sheng, S. F. Chen, and S. Y. Jiang, Biophys. J. 89, 158 (2005).

    Article  Google Scholar 

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Correspondence to John L. Brash.

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Feng, W., Zhu, S., Ishihara, K. et al. Protein resistant surfaces: Comparison of acrylate graft polymers bearing oligo-ethylene oxide and phosphorylcholine side chains. Biointerphases 1, 50–60 (2006).

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