Single vesicle analysis reveals nanoscale membrane curvature selective pore formation in lipid membranes by an antiviral α-helical peptide
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 lipi...
| Main Authors: | , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2013
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| Online Access: | https://hdl.handle.net/10356/101429 http://hdl.handle.net/10220/11090 |
| _version_ | 1826113585740251136 |
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| author | Zhdanov, Vladimir P. Tabaei, Seyed R. Rabe, Michael Cho, Nam-Joon Höök, Fredrik |
| author2 | School of Materials Science & Engineering |
| author_facet | School of Materials Science & Engineering Zhdanov, Vladimir P. Tabaei, Seyed R. Rabe, Michael Cho, Nam-Joon Höök, Fredrik |
| author_sort | Zhdanov, Vladimir P. |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T03:25:38Z |
| format | Journal Article |
| id | ntu-10356/101429 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:25:38Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | ntu-10356/1014292020-06-01T10:21:30Z Single vesicle analysis reveals nanoscale membrane curvature selective pore formation in lipid membranes by an antiviral α-helical peptide Zhdanov, Vladimir P. Tabaei, Seyed R. Rabe, Michael Cho, Nam-Joon Höök, Fredrik School of Materials Science & Engineering 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. NMRC (Natl Medical Research Council, S’pore) 2013-07-10T03:21:21Z 2019-12-06T20:38:38Z 2013-07-10T03:21:21Z 2019-12-06T20:38:38Z 2012 2012 Journal Article Tabaei, S. R., Rabe, M., Zhdanov, V. P., Cho, N.-J., Höök, F. (2012). Single vesicle analysis reveals nanoscale membrane curvature selective pore formation in lipid membranes by an antiviral α-helical peptide. Nano Letters, 12(11), 5719-5725. https://hdl.handle.net/10356/101429 http://hdl.handle.net/10220/11090 10.1021/nl3029637 en Nano letters © 2012 American Chemical Society. |
| spellingShingle | Zhdanov, Vladimir P. Tabaei, Seyed R. Rabe, Michael Cho, Nam-Joon Höök, Fredrik Single vesicle analysis reveals nanoscale membrane curvature selective pore formation in lipid membranes by an antiviral α-helical peptide |
| title | Single vesicle analysis reveals nanoscale membrane curvature selective pore formation in lipid membranes by an antiviral α-helical peptide |
| title_full | Single vesicle analysis reveals nanoscale membrane curvature selective pore formation in lipid membranes by an antiviral α-helical peptide |
| title_fullStr | Single vesicle analysis reveals nanoscale membrane curvature selective pore formation in lipid membranes by an antiviral α-helical peptide |
| title_full_unstemmed | Single vesicle analysis reveals nanoscale membrane curvature selective pore formation in lipid membranes by an antiviral α-helical peptide |
| title_short | Single vesicle analysis reveals nanoscale membrane curvature selective pore formation in lipid membranes by an antiviral α-helical peptide |
| title_sort | single vesicle analysis reveals nanoscale membrane curvature selective pore formation in lipid membranes by an antiviral α helical peptide |
| url | https://hdl.handle.net/10356/101429 http://hdl.handle.net/10220/11090 |
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