Single vesicle analysis reveals nanoscale membrane curvature selective pore formation in lipid membranes by an antiviral α-helical peptide

S.R. Tabaei, M. Rabe, V.P. Zhdanov, N.-J. Cho, F. Höök

Research output: Contribution to journalArticlepeer-review

Abstract

Using tethered sub-100 nm lipid vesicles that mimic enveloped viruses with nanoscale membrane curvature, we have in this work designed a total internal reflection fluorescence microscopy-based single vesicle assay to investigate how an antiviral amphipathic α-helical (AH) peptide interacts with lipid membranes to induce membrane curvature-dependent pore formation and membrane destabilization. Based on a combination of statistics from single vesicle imaging, binding kinetics data, and theoretical analysis, we propose a mechanistic model that is consistent with the experimentally observed peptide association and pore formation kinetics at medically relevant peptide concentrations (10 nM to 1 μM) and unusually low peptide-to-lipid (P/L) ratio (∼1/1000). Importantly, the preference of the AH peptide to selectively rupture virions with sub-100 nm diameters appears to be related to membrane strain-dependent pore formation rather than to previously observed nanoscale membrane curvature facilitated binding of AH peptides. Compared to other known proteins and peptides, the combination of low effective P/L ratio and high specificity for nm-sized membrane curvature lends this particular AH peptide great potential to serve as a framework for developing a highly specific and potent antiviral agent for prophylactic and therapeutic applications while avoiding toxic side effects against host cell membranes.
Original languageEnglish
JournalNano Letters
DOIs
Publication statusPublished - 24 Oct 2012

Fingerprint

Dive into the research topics of 'Single vesicle analysis reveals nanoscale membrane curvature selective pore formation in lipid membranes by an antiviral α-helical peptide'. Together they form a unique fingerprint.

Cite this