Single Vesicle Analysis Reveals Nanoscale Membrane Curvature Selective Pore Formation in Lipid Membranes by an Antiviral α-Helical Peptide
Artikel i vetenskaplig tidskrift, 2012

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.

pore formation

membrane curvature

Single molecule fluorescence microscopy

antiviral peptides

lipid vesicles

peptide nucleation

Författare

Seyed Tabaei

Chalmers, Teknisk fysik, Biologisk fysik

Michael Rabe

Chalmers, Teknisk fysik, Biologisk fysik

Vladimir Zhdanov

Kompetenscentrum katalys (KCK)

N. J. Cho

Nanyang Technological University

Fredrik Höök

Chalmers, Teknisk fysik, Biologisk fysik

Nano Letters

1530-6984 (ISSN) 1530-6992 (eISSN)

Vol. 12 11 5719-5725

Styrkeområden

Nanovetenskap och nanoteknik

Livsvetenskaper och teknik

Ämneskategorier

Biologiska vetenskaper

Nanoteknik

DOI

10.1021/nl3029637

Mer information

Skapat

2017-10-07