Cross-linked self-assembling peptides and their post-assembly functionalization via one-pot and in situ gelation system

Raffaele Pugliese, Fabrizio Gelain

Research output: Contribution to journalArticlepeer-review


Supramolecular nanostructures formed through peptide self-assembly can have a wide range of applications in the biomedical landscape. However, they often lose biomechanical properties at low mechanical stress due to the non-covalent interactions working in the self-assembling process. Herein, we report the design of cross-linked self-assembling peptide hydrogels using a one-pot in situ gelation system, based on 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide/N-hydroxysulfosuccinimide (EDC/sulfo–NHS) coupling, to tune its biomechanics. EDC/sulfo–NHS coupling led to limited changes in storage modulus (from 0.9 to 2 kPa), but it significantly increased both the strain (from 6% to 60%) and failure stress (from 19 to 35 Pa) of peptide hydrogel without impairing the spontaneous formation of β-sheet-containing nano-filaments. Furthermore, EDC/sulfo–NHS cross-linking bestowed self-healing and thixotropic properties to the peptide hydrogel. Lastly, we demonstrated that this strategy can be used to incorporate bioactive functional motifs after self-assembly on pre-formed nanostructures by functionalizing an Ac-LDLKLDLKLDLK-CONH2 (LDLK12) self-assembling peptide with the phage display-derived KLPGWSG peptide involved in the modulation of neural stem cell proliferation and differentiation. The incorporation of a functional motif did not alter the peptide’s secondary structure and its mechanical properties. The work reported here offers new tools to both fine tune the mechanical properties of and tailor the biomimetic properties of self-assembling peptide hydrogels while retaining their nanostructures, which is useful for tissue engineering and regenerative medicine applications.

Original languageEnglish
Article number4261
Pages (from-to)1-14
Number of pages14
JournalInternational Journal of Molecular Sciences
Issue number12
Publication statusPublished - Jun 2 2020


  • Cross-linking
  • EDC
  • Functional motifs
  • Mechanical properties
  • NHS
  • Rheology
  • Self-assembling peptides
  • Sulfo
  • Supramolecular hydrogels

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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