, Volume 3, Issue 1, pp 21–29 | Cite as

Tripeptide Self-Assembled Hydrogels: Soft Nanomaterials for Biological Applications

  • Silvia MarchesanEmail author
  • Lynne Waddington
  • Christopher D. Easton
  • Firdawosia Kushkaki
  • Keith M. McLean
  • John S. Forsythe
  • Patrick G. Hartley


Short peptide self-assembled hydrogels are a promising class of soft nanomaterials for drug delivery and regenerative medicine. Here we describe the gelation of tripeptides, consisting of d and l hydrophobic amino acids, in buffer, following a pH switch to 7.4 (i.e., physiological pH). Interestingly, tripeptide analogues consisting of l-only amino acids fail to form a gel under the same conditions. The nanostructure of these self-assembling peptides is investigated by a number of techniques (atomic force microscopy, transmission electron microscopy, and confocal light microscopy) to unveil their architectures. In addition, these self-assembled soft nanomaterials can be potentially used as vehicles to deliver bioactive molecules. For instance, we describe the incorporation into the gel of rhodamine dye as a model compound in a two-step procedure: firstly, the dye is dissolved in the gel precursor solution; secondly, dilution to a final pH of 7.4 triggers self-assembly and gelation of the system. We analyse the effect of dye incorporation within either precursor solution on the secondary structure, nanoarchitecture, and rheological properties of the resulting peptide materials. We also present data concerning dye release kinetics. Dye release is achieved within 48 h, and no burst release is observed. We anticipate that these systems will find biological applications for the delivery of bioactive compounds.


Peptide self-assembly Hydrogel Release Biomaterials 



The authors acknowledge the facilities of Monash Micro Imaging, Monash University, Australia, and in particular Stephen Firth, Dr. Judy Callaghan and Dr. Alex Fulcher for their scientific and technical assistance. The authors also acknowledge the CSIRO-Monash University Collaborative Research Support Scheme (CRSS) for funding.

Supplementary material

12668_2012_74_MOESM1_ESM.doc (15.6 mb)
ESM 1 DOC 15.5 mb

MPEG 6,732 kb


  1. 1.
    Hamidi, M., Azadi, A., & Rafiei, P. (2008). Hydrogel nanoparticles in drug delivery. Advanced Drug Delivery Reviews, 60, 1638–49.CrossRefGoogle Scholar
  2. 2.
    Chung, H. J., & Park, T. G. (2009). Self-assembled and nanostructured hydrogels for drug delivery and tissue engineering. Nano Today, 4, 429–37.CrossRefGoogle Scholar
  3. 3.
    Hendrickson, G. R., Smith, M. H., South, A. B., & Lyon, L. A. (2010). Design of multiresponsive hydrogel particles and assemblies. Adv Funct Mat, 20(11), 1697–712.CrossRefGoogle Scholar
  4. 4.
    Smith, M. H., & Lyon, L. A. (2012). Multifunctional nanogels for siRNA delivery. Accounts of Chemical Research, 45, 985–93.CrossRefGoogle Scholar
  5. 5.
    Luo, Z., & Zhang, S. (2012). Designer nanomaterials using chiral self-assembling peptide systems and their emerging benefit for society. Chemical Society Reviews, 41, 4736–54.CrossRefGoogle Scholar
  6. 6.
    Kopeček, J., & Yang, J. (2009). Peptide-directed self-assembly of hydrogels. Acta Biomaterialia, 5, 805–16.CrossRefGoogle Scholar
  7. 7.
    Adams, D. J. (2011). Dipeptide and tripeptide conjugates as low-molecular-weight hydrogelators. Macromolecular Bioscience, 11, 160–73.CrossRefGoogle Scholar
  8. 8.
    Smith, A. M., Williams, R. J., Tang, C., Coppo, P., Collins, R. F., Turner, M. L., et al. (2008). Fmoc-diphenylalanine self assembles to a hydrogel via a novel architecture based on pi-pi interlocked beta-sheets. Advanced Materials, 20, 37.CrossRefGoogle Scholar
  9. 9.
    Chen, L., Revel, S., Morris, K., Serpell, L. C., & Adams, D. J. (2010). Effect of molecular structure on the properties of naphthalene-dipeptide hydrogelators. Langmuir, 26, 13466–71.CrossRefGoogle Scholar
  10. 10.
    Mishra, A., Loo, Y. H., Deng, R. S., Chuah, Y. J., Hee, H. T., Ying, J. Y., et al. (2011). Ultrasmall natural peptides self-assemble to strong temperature-resistant helical fibers in scaffolds suitable for tissue engineering. Nano Today, 6, 438.CrossRefGoogle Scholar
  11. 11.
    Orbach, R., Adler-Abramovich, L., Zigerson, S., Mironi-Harpaz, I., Seliktar, D., & Gazit, E. (2009). Self-assembled Fmoc-peptides as a platform for the formation of nanostructures and hydrogels. Biomacromol, 10, 2646–51.CrossRefGoogle Scholar
  12. 12.
    Panda, J. J., Dua, R., Mishra, A., Mittra, B., & Chauhan, V. S. (2012). 3D cell growth and proliferation on a RGD functionalized nanofibrillar hydrogel based on a conformationally restricted residue containing dipeptide. ACS Applied Materials & Interfaces, 2, 2839–48.CrossRefGoogle Scholar
  13. 13.
    Wang, H. M., Yang, C. H., Tan, M., Wang, L., Kong, D. L., & Yang, Z. M. (2011). A structure-gelation ability study in a short peptide-based 'Super Hydrogelator' system. Soft Matter, 7, 3897–905.CrossRefGoogle Scholar
  14. 14.
    Marchesan, S., Easton, C. D., Kushkaki, F., Waddington, L., & Hartley, P. G. (2012). Tripeptide self-assembled hydrogels: unexpected twists of chirality. Chemical Communications (Cambridge, England), 48, 2195–7.CrossRefGoogle Scholar
  15. 15.
    Marchesan, S., Waddington, L., Easton, C. D., Winkler, D. A., Goodall, L., Forsythe, J., et al. (2012). Unzipping the role of chirality in nanoscale self-assembly of tripeptide hydrogels. Nanoscale, 4, 6752–60.CrossRefGoogle Scholar
  16. 16.
    Castelletto, V., Hamley, I. W., Stain, C., & Connon, C. (2012). Slow-release RGD-peptide hydrogel monoliths. Langmuir, 28, 12575–80.CrossRefGoogle Scholar
  17. 17.
    Shea, J. E., Wu, C., Biancalana, M., & Koide, S. (2009). Binding modes of thioflavin-T to the single-layer beta-sheet of the peptide self-assembly mimics. Journal of Molecular Biology, 394, 627–33.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Silvia Marchesan
    • 1
    Email author
  • Lynne Waddington
    • 1
  • Christopher D. Easton
    • 1
  • Firdawosia Kushkaki
    • 2
  • Keith M. McLean
    • 1
  • John S. Forsythe
    • 3
  • Patrick G. Hartley
    • 1
  1. 1.CSIRO Materials Science and EngineeringClaytonAustralia
  2. 2.Department of ChemistryLa Trobe UniversityBundooraAustralia
  3. 3.Department of Materials EngineeringMonash UniversityClaytonAustralia

Personalised recommendations