title: Controlled biodegradation of self-assembling β-hairpin peptide hydrogels by proteolysis with matrix metalloproteinase-13.
abstract: Controlled biodegradation specific to matrix metalloproteinase-13 was incorporated into the design of self-assembling β-hairpin peptide hydrogels. Degrading Peptides (DP peptides) are a series of five peptides that have varying proteolytic susceptibilities toward MMP-13. These peptides undergo environmentally triggered folding and self-assembly under physiologically relevant conditions (150 mm NaCl, pH 7.6) to form self-supporting hydrogels. In the presence of enzyme, gels prepared from distinct peptides are degraded at rates that differ according to the primary sequence of the single peptide comprising the gel. Material degradation was monitored by oscillatory shear rheology over the course of 14 days, where overall degradation of the gels vary from 5% to 70%. Degradation products were analyzed by HPLC and identified by electrospray-ionization mass spectrometry. This data shows that proteolysis of the parent peptides constituting each gel occurs at the intended sequence location. DP hydrogels show specificity to MMP-13 and are only minimally cleaved by matrix metalloproteinase-3 (MMP-3), another common enzyme present during tissue injury. In vitro migration assays performed with SW1353 cells show that migration rates through each gel differs according to peptide sequence, which is consistent with the proteolysis studies using exogenous MMP-13.
authors.affiliation: National Cancer Institute, Center for Cancer Research, Frederick, MD 21701, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Giano
authors.forename: Darrin J
authors.initials: DJ
authors.lastname: Pochan
authors.forename: Joel P
authors.initials: JP
authors.lastname: Schneider
mesh_terms: D000595:Amino Acid Sequence; D001673:Biodegradation, Environmental; D045744:Cell Line, Tumor; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary; D012212:Rheology
chemical_list: D020100:Hydrogels; D010455:Peptides; D053509:Matrix Metalloproteinase 13