title: Deciphering How Pore Formation Causes Strain-Induced Membrane Lysis of Lipid Vesicles.
abstract: Pore formation by membrane-active antimicrobial peptides is a classic strategy of pathogen inactivation through disruption of membrane biochemical gradients. It remains unknown why some membrane-active peptides also inhibit enveloped viruses, which do not depend on biochemical gradients. Here, we employ a label-free biosensing approach based on simultaneous quartz crystal microbalance-dissipation and ellipsometry measurements in order to investigate how a pore-forming, virucidal peptide destabilizes lipid vesicles in a surface-based experimental configuration. A key advantage of the approach is that it enables direct kinetic measurement of the surface-bound peptide-to-lipid (P:L) ratio. Comprehensive experiments involving different bulk peptide concentrations and biologically relevant membrane compositions support a unified model that membrane lysis occurs at or above a critical P:L ratio, which is at least several-fold greater than the value corresponding to the onset of pore formation. That is consistent with peptide-induced pores causing additional membrane strain that leads to lysis of highly curved membranes. Collectively, the work presents a new model that describes how peptide-induced pores may destabilize lipid membranes through a membrane strain-related lytic process, and this knowledge has important implications for the design and application of membrane-active peptides.
authors.affiliation: School of Materials Science and Engineering and Centre for Biomimetic Sensor Science, Nanyang Technological University , 50 Nanyang Drive 637553, Singapore.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Jackman
authors.affiliation: School of Materials Science and Engineering and Centre for Biomimetic Sensor Science, Nanyang Technological University , 50 Nanyang Drive 637553, Singapore.
authors.forename: Haw Zan
authors.initials: HZ
authors.lastname: Goh
authors.affiliation: School of Materials Science and Engineering and Centre for Biomimetic Sensor Science, Nanyang Technological University , 50 Nanyang Drive 637553, Singapore.|Boreskov Institute of Catalysis, Russian Academy of Sciences , Novosibirsk 630090, Russia.
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Zhdanov
authors.affiliation: School of Materials Science and Engineering and Centre for Biomimetic Sensor Science, Nanyang Technological University , 50 Nanyang Drive 637553, Singapore.|Austrian Institute of Technology (AIT) , Donau-City-Strasse 1, 1220 Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Knoll
authors.affiliation: School of Materials Science and Engineering and Centre for Biomimetic Sensor Science, Nanyang Technological University , 50 Nanyang Drive 637553, Singapore.|School of Chemical and Biomedical Engineering, Nanyang Technological University , 62 Nanyang Drive 637459, Singapore.
authors.forename: Nam-Joon
authors.initials: NJ
authors.lastname: Cho
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D008567:Membranes, Artificial; D013499:Surface Properties
chemical_list: D000890:Anti-Infective Agents; D008055:Lipids; D008567:Membranes, Artificial