Shear-Thinning and Rapid-Recovery Peptide Hydrogel for Biomedical Applications

Abstract

Peptides have become attractive molecules for fabricating biomaterials. Studies of peptide structure, assembly properties, and dynamic behavior in response to external parameters have led to rational novel design of peptide biomaterials. One model sequence selected was a β-spiral motif of spider flagelliform silk protein, [GPGGX]n (X = any amino acid). Modifying the X residue can change the quantity of secondary structure and the stability of this spider silk motif. Glycine provides flexible properties, and proline influences the secondary structure and mechanical properties. Another model sequence was GXGXDXUX (U = hydrophobic residue), a Ca2+ binding domain of lipase Lip A from Serratia marcescens, in which aspartate residue is required for ion binding. Combining with [GPGGX]n, we rationally designed peptide as GPGGDGPGGD (eD2). The Ca2+ binding sequence was hidden in the first eight residues of eD2. As expected, this peptide can assemble into nanofibrils triggered by Ca2+ ions. Using the segment FLIVIGSII (h9) from the third trans-membrane segment of subunit IV in the dihydropyridine sensitive human muscle L-type calcium channel as the hydrophobic motif, we obtained FLIVIGSIIGPGGDGPGGD (h9e) peptide. The h9e self-assembled into nanofibrils and further formed shear-thinning and rapid recovery hydrogel in neutral pH range from 6.0 to 8.0 with a large working range of temperature. NMR study showed that amphiphilic structure of h9e peptide tended to adopt a more helical structure during hydrogel formation. The h9e peptide has great potential for biomedical applications. MCF-7 cells were successfully grown as colony-like clusters (reminiscent of real tumors) in h9e hydrogel system. The drug response test of cisplatin further demonstrated the capability of h9e system for drug screen. Moreover, h9e hydrogel showed a promising adjuvanticity by enhancing the vaccine efficacy for killed H1N1 swine influenza virus and PRRS modified live virus.

This is a preview of subscription content, access via your institution.

References

  1. 1.

    F. Cui ; Y. Li ; J Ge. Mat. Sci. Eng. R-Reports 2007, 57, 1–27.

    Article  CAS  Google Scholar 

  2. 2.

    N. Cho ; J. A. Jackman ; M. Liu ; C. W Frank. Langmuir 2011, 27, 3739–3748.

    CAS  Article  Google Scholar 

  3. 3.

    I. Morgado ; M Faendrich. Curr. Opin. Col. Int. Sci. 2011, 16, 508–514.

    CAS  Article  Google Scholar 

  4. 4.

    X. S. J Sun. Bio. Mat. Bio. 2011, 5, 409–432.

    CAS  Google Scholar 

  5. 5.

    K. A. Afonin ; W. W. Grabow ; F. M. Walker ; E. Bindewald ; M. A. Dobrovolskaia ; B. A. Shapiro ; L Jaeger. Nat. Prot. 2011, 6, 2022–2034.

    CAS  Article  Google Scholar 

  6. 6.

    A. Junk ; F Riess. Am. J. Phy. 2006, 74, 825–830.

    CAS  Article  Google Scholar 

  7. 7.

    W Madia. Mater. Sci. 2006, 37A, 2905–2918.

    CAS  Google Scholar 

  8. 8.

    V. T. Yadugiri ; R Malhotra. Curr. Sci. 2010, 99, 900–907.

    Google Scholar 

  9. 9.

    C. A. E. Hauser ; S Zhang. Chem. Soc. Rev. 2010, 39, 2780–2790.

    CAS  Article  Google Scholar 

  10. 10.

    M. R. Caplan ; P. N. Moore ; S. G. Zhang ; R. D. Kamm ; D. A Lauffenburger. Biomacromolecules 2000, 1, 627–631.

    CAS  Article  Google Scholar 

  11. 11.

    F. Gelain ; A. Lomander ; A. L. Vescovi ; S. J Zhang. Nanosci. Nanotech. 2007, 7, 424–434.

    CAS  Article  Google Scholar 

  12. 12.

    S. Zhang ; C. Lockshin ; A. Herbert ; E. Winter ; A Rich. EMBO J. 1992 11 3787 3796

    CAS  Article  Google Scholar 

  13. 13.

    S. Zhang ; T. Holmes ; C. Lockshin ; Rich, Proc. Natl. Acad. Sci. U. S. A. 1993, 90, 3334–3338.

    CAS  Article  Google Scholar 

  14. 14.

    Y. Loo ; S. Zhang ; C. A. E Hauser. Biotechnol. Adv. 2012, 30, 593–603.

    CAS  Article  Google Scholar 

  15. 15.

    Z. Luo ; S. Wang ; S. Zhang Biomaterials 2011, 32, 2013–2020.

    CAS  Article  Google Scholar 

  16. 16.

    U. Khoe ; Y. Yang ; S Zhang. Langmuir 2009, 25, 4111–4114.

    CAS  Article  Google Scholar 

  17. 17.

    M. Ryadnov ; D Woolfson. Nature Materials 2003, 2, 329–332.

    CAS  Article  Google Scholar 

  18. 18.

    J. Hartgerink ; E Beniash.; Stupp, S Science 2001, 294, 1684–1688.

    CAS  Google Scholar 

  19. 19.

    J. Schneider ; D. Pochan ; B. Ozbas ; K. Rajagopal ; L. Pakstis ; J. J Kretsinger. Am. Chem. Soc. 2002, 124, 15030–15037.

    CAS  Article  Google Scholar 

  20. 20.

    J. R. McDaniel ; D. J. Callahan ; A Chilkoti. Adv. Drug Deliv. Rev. 2010, 62, 1456–1467.

    CAS  Article  Google Scholar 

  21. 21.

    P. Ringler ; G Schulz. Science 2003, 302, 106–109.

    CAS  Article  Google Scholar 

  22. 22.

    R. P. Nagarkar ; R. A. Hule ; D. J. Pochan ; J. P Schneider. Biopolymers 2010, 94, 141–155.

    CAS  Article  Google Scholar 

  23. 23.

    S. Garty ; N. Kimelman-Bleich ; Z. Hayouka ; D. Cohn ; A. Friedler ; G. Pelled ; D Gazit. Biomacromolecules 2010, 11, 1516–1526.

    CAS  Article  Google Scholar 

  24. 24.

    K. Chawla ; T. Yu ; S. W. Liao ; Z Guan. Biomacromolecules 2011, 12, 560–567.

    CAS  Article  Google Scholar 

  25. 25.

    S Zhang. Wet or let die. Nat. Mater. 2004, 3, 7–8.

    CAS  Article  Google Scholar 

  26. 26.

    I. Massodi ; S. Moktan ; A Rawat.; L. Bidwell, Gene III ; D Raucher. Int. J. Cancer 2010, 126, 533–544.

    CAS  Article  Google Scholar 

  27. 27.

    A. Aggeli ; M. Bell ; L. Carrick ; C. Fishwick ; R. Harding ; P. Mawer ; S. Radford ; A. Strong ; N. J Boden. Am. Chem. Soc. 2003, 125, 9619–9628.

    CAS  Article  Google Scholar 

  28. 28.

    M. B. Charati ; I. Lee ; K. C. Hribar ; J. A Burdick. Small 2010, 6, 1608–1611.

    CAS  Article  Google Scholar 

  29. 29.

    E. Dawson ; G. Mapili ; K. Erickson ; S. Taqvi ; K Roy. Adv. Drug Deliv. Rev. 2008, 60, 215–228.

    CAS  Article  Google Scholar 

  30. 30.

    S. Koutsopoulos ; L. D. Unsworth ; Y. Nagaia ; S Zhang. Proc. Natl. Acad. Sci. U. S. A. 2009, 106, 4623–4628.

    CAS  Article  Google Scholar 

  31. 31.

    C. Chen ; F. Pan ; S. Zhang ; J. Hu ; M. Cao ; J. Wang ; H. Xu ; X. Zhao ; J. R Lu. Biomacromolecules 2010, 11, 402–411.

    CAS  Article  Google Scholar 

  32. 32.

    M. Kanlayavattanakul ; N Lourith. Lipopeptides in cosmetics. Inter. J. Cosm. Sci. 2010, 32, 1–8.

    CAS  Article  Google Scholar 

  33. 33.

    E. Dawson ; G. Mapili ; K. Erickson ; S. Taqvi ; K Roy. Adv. Drug Deliv. Rev. 2008, 60, 215–228.

    CAS  Article  Google Scholar 

  34. 34.

    C. Feder-Mengus ; S. Ghosh ; A. Reschner ; I. Martin ; G. C Spagnoli. Trends Mol. Med. 2008, 14, 333–340.

    CAS  Article  Google Scholar 

  35. 35.

    C. Yan ; D. J Pochan. Chem. Soc. Rev. 2010, 39, 3528–3540.

    CAS  Article  Google Scholar 

  36. 36.

    M. C. Cushing ; K. S Anseth. Science 2007, 316, 1133–1134

    CAS  Article  Google Scholar 

  37. 37.

    H. Kleinman ; G Martin. Cancer Biol. 2005, 15, 378–386.

    CAS  Article  Google Scholar 

  38. 38.

    A. M. McGrath ; L. N. Novikova ; L. N. Novikova ; M Wiberg. BD (TM) Brain Res. Bull. 2010, 83, 207–213.

    CAS  Article  Google Scholar 

  39. 39.

    M. Zhou ; A. M. Smith ; A. K. Das ; N. W. Hodson ; R. F. Collins ; R. V. Ulijn ; J. E Gough. Biomaterials 2009, 30, 2523–2530.

    CAS  Article  Google Scholar 

  40. 40.

    L. Haines-Butterick ; K. Rajagopal ; M. Branco ; D. Salick ; R. Rughani ; M. Pilarz ; M. S. Lamm ; D. J. Pochan ; J. P Schneider. Proc. Natl. Acad. Sci. U. S. A. 2007, 104, 7791–7796.

    CAS  Article  Google Scholar 

  41. 41.

    R. George ; J Heringa. Protein Eng. 2002, 15, 871–879.

    CAS  Article  Google Scholar 

  42. 42.

    M. Levitt ; C Chothia. Nature 1976, 261, 552–558.

    CAS  Article  Google Scholar 

  43. 43.

    C. Angkawidjaja ; A. Paul ; Y. Koga ; K. Takano ; S Kanava. FEBS letters 2005, 579, 4707.

    CAS  Article  Google Scholar 

  44. 44.

    Y. Yamada ; K. Hozumi ; A. Aso ; A. Hotta ; K. Toma ; F. Katagiri ; Y. Kikkawa ; M Nomizu. Biomaterials 2012, 33, 4118–4125.

    CAS  Article  Google Scholar 

  45. 45.

    K Okuyama. Biopolymers 2009, 91, 361–372.

    CAS  Article  Google Scholar 

  46. 46.

    Megeed. Adv. Drug Deliv. Rev. 2002, 54, 1075.

  47. 47.

    J. L. Gifford ; M. P. Walsh ; H. J Vogel. Biochem. J. 2007, 405, 199–221.

    CAS  Article  Google Scholar 

  48. 48.

    M. R. Nelson ; W. J Chazin. Biometals 1998, 11, 297–318.

    CAS  Article  Google Scholar 

  49. 49.

    H. Huang ; X Sun. Biomacromolecules, 2010, 11, 3390–3394.

    CAS  Article  Google Scholar 

  50. 50.

    H. Huang ; J. Shi ; J. Laskin ; Z. Liu ; D. S. McVey ; X Sun. Soft Matter, 2011, 7, 8905–8912.

    CAS  Article  Google Scholar 

  51. 51.

    X. Shen ; X. Mo ; R. Moore ; S. J. Frazier ; T. Iwamoto ; J. M. Tomich et al. J. Nanosci. Nanotechnol. 2006, 6, 837–844.

    CAS  Article  Google Scholar 

  52. 52.

    X. Mo ; Y. Hiromasa ; M. Warner ; A. N. Al-Rawi ; T. Iwamoto ; T. S. Rahman et al. Biophys. J. 2008, 94, 1807–1817.

    CAS  Article  Google Scholar 

  53. 53.

    H. Huang ; A. I. Herrera ; Z. Luo ; O. Prakash ; X Sun. Biophysical Journal. 2012, 103, 979–988.

    CAS  Article  Google Scholar 

  54. 54.

    H. Huang ; Y. Ding ; X. Sun ; T. A Nguyen. PLOS ONE, 2013, e59482.

    Google Scholar 

  55. 55.

    X. Li ; A.J. Galliher-Beckley ; J.C. Nietfeld, H. Huang ; X. Sun ; K.S. Faaberg ; J Shi. Vaccine, 2013, 31, 4508–4515.

    CAS  Article  Google Scholar 

  56. 56.

    G Kelter, NJ Sweeney, K Strohfeldt, HH Fiebig. Tacke MAnticancer Drug, 2005, 16: 1091–1098.

    CAS  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Xiuzhi Susan Sun.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Huang, H.J., Sun, X.S. Shear-Thinning and Rapid-Recovery Peptide Hydrogel for Biomedical Applications. MRS Online Proceedings Library 1622, 175–188 (2013). https://doi.org/10.1557/opl.2014.379

Download citation