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

  • Hongzhou John Huang (a1) and Xiuzhi Susan Sun (a1)

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.

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1. Cui F.; Li Y.; Ge J. Mat. Sci. Eng. R-Reports 2007, 57, 127.
2. Cho N.; Jackman J. A.; Liu M.; Frank C. W. Langmuir 2011, 27, 37393748.
3. Morgado I.; Faendrich M. Curr. Opin. Col. Int. Sci. 2011, 16, 508514.
4. Sun X. S. J. Bio. Mat. Bio. 2011, 5, 409432.
5. Afonin K. A.; Grabow W. W.; Walker F. M.; Bindewald E.; Dobrovolskaia M. A.; Shapiro B. A.; Jaeger L. Nat. Prot. 2011, 6, 20222034.
6. Junk A.; Riess F. Am. J. Phy. 2006, 74, 825830.
7. Madia W. Mater. Sci. 2006, 37A, 29052918.
8. Yadugiri V. T.; Malhotra R. Curr. Sci. 2010, 99, 900907.
9. Hauser C. A. E.; Zhang S. Chem. Soc. Rev. 2010, 39, 27802790.
10. Caplan M. R.; Moore P. N.; Zhang S. G.; Kamm R. D.; Lauffenburger D. A. Biomacromolecules 2000, 1, 627631.
11. Gelain F.; Lomander A.; Vescovi A. L.; Zhang S. J. Nanosci. Nanotech. 2007, 7, 424434.
12. Zhang S.; Lockshin C.; Herbert A.; Winter E.; Rich A. EMBO J. 1992 11 3787 3796
13. Zhang S.; Holmes T.; Lockshin C.; Rich , Proc. Natl. Acad. Sci. U. S. A. 1993, 90, 33343338.
14. Loo Y.; Zhang S.; Hauser C. A. E. Biotechnol. Adv. 2012, 30, 593603.
15. Luo Z.; Wang S.; Zhang S. Biomaterials 2011, 32, 20132020.
16. Khoe U.; Yang Y.; Zhang S. Langmuir 2009, 25, 41114114.
17. Ryadnov M.; Woolfson D. Nature Materials 2003, 2, 329332.
18. Hartgerink J.; Beniash E.; Stupp, S Science 2001, 294, 16841688.
19. Schneider J.; Pochan D.; Ozbas B.; Rajagopal K.; Pakstis L.; Kretsinger J. J. Am. Chem. Soc. 2002, 124, 1503015037.
20. McDaniel J. R.; Callahan D. J.; Chilkoti A. Adv. Drug Deliv. Rev. 2010, 62, 14561467.
21. Ringler P.; Schulz G. Science 2003, 302, 106109.
22. Nagarkar R. P.; Hule R. A.; Pochan D. J.; Schneider J. P. Biopolymers 2010, 94, 141155.
23. Garty S.; Kimelman-Bleich N.; Hayouka Z.; Cohn D.; Friedler A.; Pelled G.; Gazit D. Biomacromolecules 2010, 11, 15161526.
24. Chawla K.; Yu T.; Liao S. W.; Guan Z. Biomacromolecules 2011, 12, 560567.
25. Zhang S. Wet or let die. Nat. Mater. 2004, 3, 78.
26. Massodi I.; Moktan S.; Rawat A.; Bidwell , Gene L. III; Raucher D. Int. J. Cancer 2010, 126, 533544.
27. Aggeli A.; Bell M.; Carrick L.; Fishwick C.; Harding R.; Mawer P.; Radford S.; Strong A.; Boden N. J. Am. Chem. Soc. 2003, 125, 96199628.
28. Charati M. B.; Lee I.; Hribar K. C.; Burdick J. A. Small 2010, 6, 16081611.
29. Dawson E.; Mapili G.; Erickson K.; Taqvi S.; Roy K. Adv. Drug Deliv. Rev. 2008, 60, 215228.
30. Koutsopoulos S.; Unsworth L. D.; Nagaia Y.; Zhang S. Proc. Natl. Acad. Sci. U. S. A. 2009, 106, 46234628.
31. Chen C.; Pan F.; Zhang S.; Hu J.; Cao M.; Wang J.; Xu H.; Zhao X.; Lu J. R. Biomacromolecules 2010, 11, 402411.
32. Kanlayavattanakul M.; Lourith N. Lipopeptides in cosmetics. Inter. J. Cosm. Sci. 2010, 32, 18.
33. Dawson E.; Mapili G.; Erickson K.; Taqvi S.; Roy K. Adv. Drug Deliv. Rev. 2008, 60, 215228.
34. Feder-Mengus C.; Ghosh S.; Reschner A.; Martin I.; Spagnoli G. C. Trends Mol. Med. 2008, 14, 333340.
35. Yan C.; Pochan D. J. Chem. Soc. Rev. 2010, 39, 35283540.
36. Cushing M. C.; Anseth K. S. Science 2007, 316, 11331134
37. Kleinman H.; Martin G. Cancer Biol. 2005, 15, 378386.
38. McGrath A. M.; Novikova L. N.; Novikova L. N.; Wiberg M. BD (TM) Brain Res. Bull. 2010, 83, 207213.
39. Zhou M.; Smith A. M.; Das A. K.; Hodson N. W.; Collins R. F.; Ulijn R. V.; Gough J. E. Biomaterials 2009, 30, 25232530.
40. Haines-Butterick L.; Rajagopal K.; Branco M.; Salick D.; Rughani R.; Pilarz M.; Lamm M. S.; Pochan D. J.; Schneider J. P. Proc. Natl. Acad. Sci. U. S. A. 2007, 104, 77917796.
41. George R.; Heringa J. Protein Eng. 2002, 15, 871879.
42. Levitt M.; Chothia C. Nature 1976, 261, 552558.
43. Angkawidjaja C.; Paul A.; Koga Y.; Takano K.; Kanava S. FEBS letters 2005, 579, 4707.
44. Yamada Y.; Hozumi K.; Aso A.; Hotta A.; Toma K.; Katagiri F.; Kikkawa Y.; Nomizu M. Biomaterials 2012, 33, 41184125.
45. Okuyama K. Biopolymers 2009, 91, 361372.
46. Megeed. Adv. Drug Deliv. Rev. 2002, 54, 1075.
47. Gifford J. L.; Walsh M. P.; Vogel H. J. Biochem. J. 2007, 405, 199221.
48. Nelson M. R.; Chazin W. J. Biometals 1998, 11, 297318.
49. Huang H.; Sun X. Biomacromolecules, 2010, 11, 33903394.
50. Huang H.; Shi J.; Laskin J.; Liu Z.; McVey D. S.; Sun X. Soft Matter, 2011, 7, 89058912.
51. Shen X.; Mo X.; Moore R.; Frazier S. J.; Iwamoto T.; Tomich J. M. et al. . J. Nanosci. Nanotechnol. 2006, 6, 837844.
52. Mo X.; Hiromasa Y.; Warner M.; Al-Rawi A. N.; Iwamoto T.; Rahman T. S. et al. . Biophys. J. 2008, 94, 18071817.
53. Huang H.; Herrera A. I.; Luo Z.; Prakash O.; Sun X. Biophysical Journal. 2012, 103, 979988.
54. Huang H.; Ding Y.; Sun X.; Nguyen T. A. PLOS ONE, 2013, e59482.
55. Li X.; Galliher-Beckley A.J.; Nietfeld J.C., Huang H.; Sun X.; Faaberg K.S.; Shi J. Vaccine, 2013, 31, 45084515.
56. Kelter G, Sweeney NJ, Strohfeldt K, Fiebig HH. Tacke MAnticancer Drug, 2005, 16: 10911098.
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