title: Rational design of MMP degradable peptide-based supramolecular filaments.
abstract: One-dimensional nanostructures formed by self-assembly of small molecule peptides have been extensively explored for use as biomaterials in various biomedical contexts. However, unlike individual peptides that can be designed to be specifically degradable by enzymes/proteases of interest, their self-assembled nanostructures, particularly those rich in β-sheets, are generally resistant to enzymatic degradation because the specific cleavage sites are often embedded inside the nanostructures. We report here on the rational design of β-sheet rich supramolecular filaments that can specifically dissociate into less stable micellar assemblies and monomers upon treatment with matrix metalloproteases-2 (MMP-2). Through linkage of an oligoproline segment to an amyloid-derived peptide sequence, we first synthesized an amphiphilic peptide that can undergo a rapid morphological transition in response to pH variations. We then used MMP-2 specific peptide substrates as multivalent cross-linkers to covalently fix the amyloid-like filaments in the self-assembled state at pH 4.5. Our results show that the cross-linked filaments are stable at pH 7.5 but gradually break down into much shorter filaments upon cleavage of the peptidic cross-linkers by MMP-2. We believe that the reported work presents a new design platform for the creation of amyloid-like supramolecular filaments responsive to enzymatic degradation.
authors.affiliation: Department of Chemical and Biomolecular Engineering and ‡Institute for NanoBiotechnology, The Johns Hopkins University 3400 North Charles Street, Baltimore, Maryland 21218, United States.
authors.forename: Yi-An
authors.initials: YA
authors.lastname: Lin
authors.forename: Yu-Chuan
authors.initials: YC
authors.lastname: Ou
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Cheetham
authors.forename: Honggang
authors.initials: H
authors.lastname: Cui
mesh_terms: D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D006863:Hydrogen-Ion Concentration; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism*; D008970:Molecular Weight; D049329:Nanostructures / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D015202:Protein Engineering / Q000379:methods*; D017433:Protein Structure, Secondary; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D010455:Peptides; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2