Self-Assembled Peptide Nanofibrils Designed to Release Membrane-Lysing Antimicrobial Peptides

Abstract

Membrane-disrupting antimicrobial peptides continue to attract increasing attention due to their potential to combat multidrug-resistant bacteria. However, some limitations are found in the success of clinical setting-based antimicrobial peptide agents, for instance, the poor stability of antimicrobial peptides in vivo and their short-term activity. Self-assembled peptide materials can improve the stability of antimicrobial peptides, but the biosafety of peptide-based materials is the main concern, although they are considered to be biocompatible, because some peptide aggregates would possibly induce protein misfolding, which could be related to amyloid-related diseases. Therefore, in this work, we designed two peptides and constructed peptide-based nanofibrils by self-assembly before its utilization. It is found that the fibrils could release the antimicrobial peptide by disassembly for microbial membrane lysis in the presence of bacteria. The designed peptide-based fibrils presented a good and long-term antimicrobial activity with bacterial membrane disruption and the efflux of calcium from bacteria. Furthermore, it could be used to construct hybrid macrofilms displaying low cytotoxicity, low hemolytic activity, and good biocompatibility. The innovative design strategy could be beneficial for the development of smart antimicrobial nanomaterials.

The Potential of Modified and Multimeric Antimicrobial Peptide Materials as Superbug Killers

“…This approach modifies the native AMP to alter its chemical characteristics (see Sections 2 and 3 , this review) so that under specific environmental conditions the peptides self-assemble/aggregate. These self-assembled multimers can form micelles (DP7-C), nanofibers ((QL) 6 -Melittin + (QL) 6 -K), lamellae (V 4 D) or fibrils (K 3 (FA) 4 K 3 ) ( Chen Y.-F. et al, 2019 ; Kornmueller et al, 2018 ; Sha et al, 2020 ; Zhang et al, 2018 ). To aid peptide self-assembly, AMP sequences can be modified or conjugated to self-assembling sequences or hydrophobic moieties (e.g., lipids or alkyl chains).…”

pH- and concentration-dependent supramolecular assembly of a fungal defensin plectasin variant into helical non-amyloid fibrils

“…5e ). Thioflavin T (ThT) is widely used to follow amyloid fibril formation via fluorescence measurements 45 and has shown potential to follow other types of protein fibrils 64 , 65 . Insulin, which is known to form amyloid fibrils upon shaking at 40 °C 79 , was used as a positive control.…”

“…Supramolecular assembling peptides have served as an inspiration for the design of new peptides with the desired functionality 37 – 42 . The study of anti-microbial polymers has mainly focused on their synthetic design to overcome challenges in immunogenicity, off-target effects and serum instability and ensure their controlled release 43 – 45 . The most prominent self-assembling AMPs are the MAX peptides, a group of designed peptides, that form an injectable hydrogel by undergoing a transition from an unstructured soluble form to a self-assembling β-hairpin 46 – 53 .…”

Self-Assembly of Nicotinic Acid-Conjugated Selenopeptides into Mesotubes

“…Molecular self-assembly of biomolecules renders a route to nanofabrication and is an excellent chemical methodology to design a new class of nanostructured materials. − Proteins and peptides, as building blocks for supramolecular self-assemblies, are particularly important for the fabrication of different biomimetic functional materials. , Contrary to complex protein molecules, small peptides have more control over the different noncovalent interactions responsible for the formation of self-assembled supramolecular structures. , The ease of peptide synthesis and manipulation as well as control over peptide length enable fabrication of different nanostructured materials such as nanofibers, nanoribbons, nanotubes, nanorods, and vesicles having different sizes and properties. − Such self-assemblies are commonly used to produce different soft biogenic materials with various tunable properties in nanotechnology and medicine. − For example, the pendent groups on the surface of self-assembled peptide nanocarriers have been tuned for site-specific drug delivery. , It has also been demonstrated that the assembly inspired from Aβ 42 peptide can be used to provide a scaffold for stem cell differentiation . In addition, the nanoscale peptide assembly has been reported to exhibit significant pyroelectric activity along with other physical properties. ,− …”