Rational Design of MMP Degradable Peptide-Based Supramolecular
Filaments
- Publication date
- Publisher
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