Author(s): Ferreira , Daniela S. ; Lin, Yi-An ; Cui, Honggang ; Hubbell, Jeffrey A. ; Reis, R. L. ; Azevedo, Helena S.
Date: 2015
Persistent ID: http://hdl.handle.net/1822/32358
Origin: RepositóriUM - Universidade do Minho
Subject(s): Degradation; Enzyme-responsive materials; Hyaluronan; Matrix metalloproteinase-1; Peptide amphiphiles; Self-assembling membranes; Science & Technology
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.
This work was funded by the European Regional Development Fund (ERDF) through the Operational Competitiveness Programme "COMPETE" (FCOMP-01-0124-FEDER-014758) and national funds through the Portuguese Foundation for Science and Technology (FCT) under the project PTDC/EBB-BIO/114523/2009. The authors also thank a start-up grant provided by the School of Engineering and Materials Science at QMUL. D.S.F. gratefully acknowledges FCT for the PhD scholarship (SFRH/BD/44977/2008).
