Molecularly engineered self-assembling membranes for cell-mediated degradation

Daniela S. Ferreira, Yi An Lin, Honggang Cui, Jeffrey A. Hubbell, Rui L. Reis, Helena S. Azevedo

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


The use of peptide engineering to develop self-assembling membranes that are responsive to cellular enzyme activities is reported. The membranes are obtained by combining hyaluronan (HA) and a rationally designed peptide amphiphile (PA) containing a proteolytic domain (GPQGIWGQ octapeptide) sensitive to matrix metalloproteinase-1 (MMP-1). Insertion of an octapeptide in a typical PA structure does not disturb its self-assembly into fibrillar nanostructures neither the ability to form membranes with HA. In vitro enzymatic degradation with hyaluronidase and MMP-1 shows that membranes containing the MMP-1 substrate exhibit enhanced enzymatic degradation, compared with control membranes (absence of MMP-1 cleavable peptide or containing a MMP-1 insensitive sequence), being completely degraded after 7 days. Cell viability and proliferation is minimally affected by the enzymatically cleavable functionality of the membrane, but the presence of MMP-1 cleavable sequence does stimulate the secretion of MMP-1 by fibroblasts and interfere with matrix deposition, particularly the deposition of collagen. By showing cell-responsiveness to biochemical signals presented on self-assembling membranes, this study highlights the ability of modulating certain cellular activities through matrix engineering. This concept can be further explored to understand the cellular remodeling process and as a strategy to develop artificial matrices with more biomimetic degradation for tissue engineering applications. Self-assembling membranes, molecularly designed with enzyme-cleavable building blocks (hyaluronan and peptide amphiphiles containing a proteolytic domain) afford cell-mediated degradation and lead to enhanced cellular colonization of the membranes. This concept can be used as a strategy to develop artificial matrices with more biomimetic degradation for tissue engineering applications.

Original languageEnglish (US)
Pages (from-to)602-612
Number of pages11
JournalAdvanced Healthcare Materials
Issue number4
StatePublished - Mar 1 2015


  • Degradation
  • Enzyme-responsive materials
  • Hyaluronan
  • Matrix metalloproteinase-1
  • Peptide amphiphiles
  • Self-assembling membranes

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science


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