title: Peptide self-assembly on cell membranes to induce cell lysis.
abstract: Self-assembling into aggregates with defined structures is a common phenomenon for many peptides at high concentrations. In this study, we found that when PTP-7b (FLGALFKALSHLL), a concentration-dependent self-assembling peptide, bound to tissue cells and accumulated on cell surfaces, it migrated and self-assembled into exosome-like aggregates at certain locations on the cell membranes. Studies using confocal microscopy and scanning electron microscopy revealed that peptide PTP-7b induced cell tissue damage through a new cell lysis mechanism that involved peptide self-assembly on cell surfaces, extracting lipids from cell membranes, and transporting peptides into the cytoplasm. Peptide self-assembly attributed greatly to peptide-cell interactions and thus the biological activity of a peptide. Because peptide self-assembly was a slow process, PTP-7b-induced cell lysis showed a biphasic behavior: a gradual viability decrease was followed by a rapid decline. These results suggest that peptide self-assembly could be equally as important as charge and secondary structure of a peptide in determining the anticancer and antibacterial activities of therapeutic peptides.
authors.affiliation: Department of Chemistry, Stevens Institute of Technology, Hoboken, NJ 07030, USA.
authors.forename: Long
authors.initials: L
authors.lastname: Chen
authors.forename: Nicole
authors.initials: N
authors.lastname: Patrone
authors.forename: Jun F
authors.initials: JF
authors.lastname: Liang
mesh_terms: D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D008958:Models, Molecular; D010316:Particle Size; D010455:Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D013499:Surface Properties
chemical_list: D010455:Peptides