title: Hydrophobic mismatch demonstrated for membranolytic peptides, and their use as molecular rulers to measure bilayer thickness in native cells.
abstract: Hydrophobic mismatch is a well-recognized principle in the interaction of transmembrane proteins with lipid bilayers. This concept was extended here to amphipathic membranolytic α-helices. Nine peptides with lengths between 14 and 28 amino acids were designed from repeated KIAGKIA motifs, and their helical nature was confirmed by circular dichroism spectroscopy. Biological assays for antimicrobial activity and hemolysis, as well as fluorescence vesicle leakage and solid-state NMR spectroscopy, were used to correlate peptide length with membranolytic activity. These data show that the formation of transmembrane pores is only possible under the condition of hydrophobic matching: the peptides have to be long enough to span the hydrophobic bilayer core to be able to induce vesicle leakage, kill bacteria, and cause hemolysis. By correlating the threshold lengths for biological activity with the biophysical results on model vesicles, the peptides could be utilized as molecular rulers to measure the membrane thickness in different cells.
authors: University of Barcelona, Faculty of Chemistry, Department of Organic Chemistry, Martí i Franquès, 1, 08028, Barcelona, Spain.
authors: Ariadna
authors: A
authors: Grau-Campistany
authors: Karlsruhe Institute of Technology (KIT), Institute of Biological Interfaces (IBG-2), POB 3640, 76021 Karlsruhe, Germany.
authors: Erik
authors: E
authors: Strandberg
authors: Karlsruhe Institute of Technology (KIT), Institute of Biological Interfaces (IBG-2), POB 3640, 76021 Karlsruhe, Germany.
authors: Parvesh
authors: P
authors: Wadhwani
authors: Karlsruhe Institute of Technology (KIT), Institute of Biological Interfaces (IBG-2), POB 3640, 76021 Karlsruhe, Germany.
authors: Johannes
authors: J
authors: Reichert
authors: Karlsruhe Institute of Technology (KIT), Institute of Biological Interfaces (IBG-2), POB 3640, 76021 Karlsruhe, Germany.
authors: Jochen
authors: J
authors: Bürck
authors: University of Barcelona, Faculty of Chemistry, Department of Organic Chemistry, Martí i Franquès, 1, 08028, Barcelona, Spain.
authors: Francesc
authors: F
authors: Rabanal
authors: 1] Karlsruhe Institute of Technology (KIT), Institute of Biological Interfaces (IBG-2), POB 3640, 76021 Karlsruhe, Germany [2] KIT, Institute of Organic Chemistry, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany.
authors: Anne S
authors: AS
authors: Ulrich
mesh_terms: D002942:Circular Dichroism; D004926:Escherichia coli / Q000187:drug effects; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000187:drug effects*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation / Q000187:drug effects*
chemical_list: D008051:Lipid Bilayers; D008565:Membrane Proteins; D010455:Peptides