title: Molecularly engineered self-assembling membranes for cell-mediated degradation.
abstract: 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.
authors.affiliation: 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4806-909, Taipas, Guimarães, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal; School of Engineering and Materials Science, Queen Mary, University of London, Mile End Road, London, E1 4NS, UK; Institute for Bioengineering, School of Basic Science, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, CH-1015, Switzerland.
authors.forename: Daniela S
authors.initials: DS
authors.lastname: Ferreira
authors.forename: Yi-An
authors.initials: YA
authors.lastname: Lin
authors.forename: Honggang
authors.initials: H
authors.lastname: Cui
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Hubbell
authors.forename: Rui L
authors.initials: RL
authors.lastname: Reis
authors.forename: Helena S
authors.initials: HS
authors.lastname: Azevedo
mesh_terms: D000595:Amino Acid Sequence; D049109:Cell Proliferation; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D008567:Membranes, Artificial; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D015202:Protein Engineering / Q000379:methods*; D059748:Proteolysis; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D016326:Extracellular Matrix Proteins; D008567:Membranes, Artificial; D010455:Peptides; D013501:Surface-Active Agents; D020781:Matrix Metalloproteinase 1
keywords: degradation; enzyme-responsive materials; hyaluronan; matrix metalloproteinase-1; peptide amphiphiles; self-assembling membranes