Single Vesicle Analysis Reveals Nanoscale Membrane Curvature Selective Pore Formation in Lipid Membranes by an Antiviral alpha-Helical Peptide Full article
Journal |
Nano Letters
ISSN: 1530-6984 , E-ISSN: 1530-6992 |
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Output data | Year: 2012, Volume: 12, Number: 11, Pages: 5719-5725 Pages count : 7 DOI: 10.1021/nl3029637 | ||||||
Tags | antiviral peptides, lipid vesicles, membrane curvature, peptide nucleation, pore formation, Single molecule fluorescence microscopy | ||||||
Authors |
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Affiliations |
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Funding (3)
1 | Swedish Research Council | 2007-5286 |
2 | National Research Foundation of Singapore | NRFF2011-01 |
3 | National Medical Research Council | CBRG11nov085 |
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 a-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 æM) 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.
Cite:
Tabaei S.R.
, Rabe M.
, Zhdanov V.P.
, Cho N-J.
, Höök F.
Single Vesicle Analysis Reveals Nanoscale Membrane Curvature Selective Pore Formation in Lipid Membranes by an Antiviral alpha-Helical Peptide
Nano Letters. 2012. V.12. N11. P.5719-5725. DOI: 10.1021/nl3029637 WOS Scopus РИНЦ
Single Vesicle Analysis Reveals Nanoscale Membrane Curvature Selective Pore Formation in Lipid Membranes by an Antiviral alpha-Helical Peptide
Nano Letters. 2012. V.12. N11. P.5719-5725. DOI: 10.1021/nl3029637 WOS Scopus РИНЦ
Dates:
Submitted: | Aug 9, 2012 |
Accepted: | Oct 18, 2012 |
Published online: | Oct 30, 2012 |
Published print: | Nov 14, 2012 |
Identifiers:
Web of science | WOS:000311244400047 |
Scopus | 2-s2.0-84869153974 |
Elibrary | 20492534 |
Chemical Abstracts | 2012:1559249 |
Chemical Abstracts (print) | 157:656568 |
OpenAlex | W2102727735 |