title: Specificity and mechanism of action of alpha-helical membrane-active peptides interacting with model and biological membranes by single-molecule force spectroscopy.
abstract: In this study, to systematically investigate the targeting specificity of membrane-active peptides on different types of cell membranes, we evaluated the effects of peptides on different large unilamellar vesicles mimicking prokaryotic, normal eukaryotic, and cancer cell membranes by single-molecule force spectroscopy and spectrum technology. We revealed that cationic membrane-active peptides can exclusively target negatively charged prokaryotic and cancer cell model membranes rather than normal eukaryotic cell model membranes. Using Acholeplasma laidlawii, 3T3-L1, and HeLa cells to represent prokaryotic cells, normal eukaryotic cells, and cancer cells in atomic force microscopy experiments, respectively, we further studied that the single-molecule targeting interaction between peptides and biological membranes. Antimicrobial and anticancer activities of peptides exhibited strong correlations with the interaction probability determined by single-molecule force spectroscopy, which illustrates strong correlations of peptide biological activities and peptide hydrophobicity and charge. Peptide specificity significantly depends on the lipid compositions of different cell membranes, which validates the de novo design of peptide therapeutics against bacteria and cancers.
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun 130012, China.|School of Life Sciences, Jilin University, Changchun 130012, China.
authors.forename: Shiyu
authors.initials: S
authors.lastname: Sun
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun 130012, China.|School of Life Sciences, Jilin University, Changchun 130012, China.
authors.forename: Guangxu
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun 130012, China.|National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China.|School of Life Sciences, Jilin University, Changchun 130012, China.
authors.forename: Yibing
authors.initials: Y
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China.
authors.forename: Mingjun
authors.initials: M
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Shan
authors.affiliation: State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China.|University of Chinese Academy of Sciences, Beijing 100049, P.R. China.
authors.forename: Hongda
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun 130012, China.|National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China.|School of Life Sciences, Jilin University, Changchun 130012, China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence / Q000187:drug effects / Q000235:genetics; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D000072756:Protein Conformation, alpha-Helical; D017433:Protein Structure, Secondary; D000072760:Single Molecule Imaging; D013329:Structure-Activity Relationship
chemical_list: D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D010455:Peptides