title: Peptide fibrils with altered stability, activity, and cell selectivity.
abstract: Peptides have some unique and superior features compared to proteins. However, the use of peptides as therapeutics is hampered by their low stability and cell selectivity. In this study, a new lytic peptide (CL-1, FLGALFRALSRLL) was constructed. Under the physiological condition, peptide CL-1 self-assembled into dynamically stable aggregates with fibrils-like structures. Aggregated CL-1 demonstrated dramatically altered activity and stability in comparison with single molecule CL-1 and other lytic peptides: when incubated with cocultured bacteria and tissue cells, CL-1 aggregates killed bacteria selectively but spared cocultured human cells; CL-1 aggregates were kept intact in human serum for more than five hours. Peptide-cell interaction studies performed on lipid monolayers and live human tissue cells revealed that in comparison with monomeric CL-1, aggregated CL-1 had decreased cell affinity and membrane insertion capability on tissue cells. A dynamic process involving aggregate dissociation and rearrangement seemed to be an essential step for membrane bound CL-1 aggregates to realize its cytotoxicity to tissue cells. Our study suggests that peptide aggregation could be as important as the charge and secondary structure of a peptide in affecting peptide-cell interactions. Controlling peptide self-assembly represents a new way to increase the stability and cell selectivity of bioactive peptides for wide biomedical applications.
authors.affiliation: Department of Chemistry, Chemical Biology, and Biomedical Engineering, Charles V. Schaefer School of Engineering and Sciences, Stevens Institute of Technology, Hoboken, New Jersey 07030, United States.
authors.forename: Long
authors.initials: L
authors.lastname: Chen
authors.forename: Jun F
authors.initials: JF
authors.lastname: Liang
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C586362:CL-1 lytic peptide; D010446:Peptide Fragments