Year: 2014
Type: article
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.
Source: Biomacromolecules
DOI: 10.1021/bm500020j
Institution: Johns Hopkins University
Language: English
Subfield: Biomaterials
Field: Materials Science
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Funders: National Science Foundation, U.S. Department of Energy, Johns Hopkins University, National Institutes of Health, Office of Science, National Cancer Institute, National Institute of General Medical Sciences, National Center for Research Resources, Division of Chemistry, Basic Energy Sciences
Awards: G102163711, G1286251239, G1505794299, G2101401529, G2287611682, G2444191204, G2587862742, G262962599, G2861946347, Purchase of a Research Grade MALDI-ToF Mass Spectrometer, G3949783963, G3975751460, G409777406, G426311843, BioCARS: A Synchroton Structural Biology Resource, BioCARS: A Synchroton Structural Biology Resource, G498139845, G5106849484, G513797252, G5387317844, G5607048534, T-32 NIH Postdoctoral Training Program in Nanotechnology for Cancer Medicine NTCM, G5910536577, G6848031779, G6918803902, G7368700025, G7583137537, G969889393, G993149817
OpenAlex ID: W2085296436