Enhanced Antibacterial Properties of Self-Assembling Peptide Amphiphiles Functionalized with Heparin-Binding Cardin-Motifs

5 years ago

Enhanced Antibacterial Properties of Self-Assembling Peptide Amphiphiles Functionalized with Heparin-Binding Cardin-Motifs

Keerthana Subramanian, Thomas J. Webster, Mian Wang, Run Chang

The emergence of antibiotic resistance in bacteria has caused many healthcare problems and social burdens. In this study, a type of self-assembled peptide amphiphiles (PA) functionalized with a heparin-binding Cardin-motif peptide (sequence (AKKARK)₂) has been designed to combat bacterial drug resistance. Above the critical micelle concentration (CMC) at 45 μM, these amphiphilic Cardin antimicrobial peptide (ACA-PA) can self-assemble into cylindrical supramolecular structures (7–10 nm in diameter) via hydrophobic interactions and β-sheet secondary conformation. The ACA-PA displays excellent antibacterial properties against both Gram-positive and Gram-negative bacteria. This work also demonstrates the effects of molecular self-assembly on antibacterial activity of peptide amphiphiles. The ACA-PA exhibits antibacterial activity on Gram-positive bacteria in a dose-dependent manner, but in the case of Gram-negative bacteria, the antibacterial potency of ACA-PA is remarkably enhanced at concentrations above the CMC. The ACA-PA has been shown to cause bacterial cytoplasmic leakage, causing localized membrane disruption in Gram-positive bacteria and blisters on disorganized membranes of Gram-negative bacteria. Therefore, these peptide-based nanoparticles have promising potential as antimicrobial agents without resorting to the use of antibiotics, and, thus, should be further studied for a wide range of biomaterial applications.

Publisher URL: http://dx.doi.org/10.1021/acsami.7b07506

DOI: 10.1021/acsami.7b07506