Multivalent Presentation of Cationic Peptides on Supramolecular Nanofibers for Antimicrobial Activity

Abstract

Noncovalent and electrostatic interactions facilitate the formation of complex networks through molecular self-assembly in biomolecules such as proteins and glycosaminoglycans. Self-assembling peptide amphiphiles (PA) are a group of molecules that can form nanofibrous structures and may contain bioactive epitopes to interact specifically with target molecules. Here, we report the presentation of cationic peptide sequences on supramolecular nanofibers formed by self-assembling peptide amphiphiles for cooperative enhanced antibacterial activity. Antibacterial properties of self-assembled peptide nanofibers were significantly higher than soluble peptide molecules with identical amino acid sequences, suggesting that the tandem presentation of bioactive epitopes is important for designing new materials for bactericidal activity. In addition, bacteria were observed to accumulate more rapidly on peptide nanofibers compared to soluble peptides, which may further enhance antibacterial activity by increasing the number of peptide molecules interacting with the bacterial membrane. The cationic peptide amphiphile nanofibers were observed to attach to bacterial membranes and disrupt their integrity. These results demonstrate that short cationic peptides show a significant improvement in antibacterial activity when presented in the nanofiber form.

Lipid membrane interactions of self-assembling antimicrobial nanofibers: effect of PEGylation

“…[1][2][3][5][6][7][8] Increased activity has been reported by Beter et al upon comparing self-assembled C 12 -VVAGKKKGRW-NH 2 and KKKGRW-NH 2 nanobers with their corresponding soluble peptide molecules. 9 Similar results were reported by Chang et al for self-assembled cylindrical nanostructures made from C 16 -V 4 K 4 functionalised with an (AKKARK) 2 heparin binding Cardin-motif, which displayed strongly enhanced activity against Gram-negative bacteria above the critical micellar concentration (CMC). In the latter case it was suggested that self-assembly promotes the bacterial cytoplasmic leakage, causing blisters on disorganized membranes of Gram-negative bacteria.…”

Self-assembly dynamics and antimicrobial activity of all l- and d-amino acid enantiomers of a designer peptide

“…The amyloids can then disrupt the cell membrane. Similar interaction between self-assembled fibers and lipid vesicles or bacterial membranes has been discovered with surfactant-like peptides 14,15 and peptide amphiphiles 16 . Different from AMPs, the membrane disrupting mechanisms of amyloids have been commonly related to peptide assembly.…”

Aggregation determines the selectivity of membrane-active anticancer and antimicrobial peptides: The case of killerFLIP

“…Overall, our data indicate that peptide aggregation should be taken into account as an additional method to vary the effective hydrophobicity of membrane-active HDPs, and therefore their cell-selectivity. Peptide aggregation or ordered self-assembly presents additional advantages, since it reduces susceptibility to proteolytic degradation, it affects the pharmacokinetics and pharmacodynamics [72,[79][80][81], and it allows the local release of a high peptide concentration at a single site in the membrane [82][83][84]. Finally, aggregates of membrane-active peptides could be even considered for the entrapment of small-molecule drugs inside the hydrophobic core of the particles, for targeted delivery [85][86], leading to the development of new therapeutic tools based on synergistic effects [87].…”