Decoding distinct membrane interactions of HIV-1 fusion inhibitors using a combined atomic force and fluorescence microscopy approach

Bibliographic Details
Main Author: Franquelim, Henri G.
Publication Date: 2013
Other Authors: Gaspar, Diana, Veiga, A. Salomé, Santos, Nuno C., Castanho, Miguel A. R. B.
Format: Article
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10451/10693
Summary: © 2013 Elsevier B.V. All rights reserved.
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spelling Decoding distinct membrane interactions of HIV-1 fusion inhibitors using a combined atomic force and fluorescence microscopy approachFusion inhibitorsEnfuvirtideT-1249Atomic force microscopyFluorescence microscopySupported lipid bilayers© 2013 Elsevier B.V. All rights reserved.Enfuvirtide and T-1249 are two potent HIV-1 fusion inhibitor peptides. Recent studies indicate that lipids play an important role in the mode of action of those bioactive molecules. Using a combined tandem atomic force microscopy (AFM)–epifluorescence microscopy approach, we studied the interaction of both enfuvirtide and T-1249 with supported lipid bilayers. Fluid (ld)-gel (so) and ld-liquid ordered (lo) phase-separated membrane systems were tested. Results, especially for T-1249, show significant lipid membrane activity at a 15 μM peptide concentration. T-1249, in opposition to enfuvirtide, induces an increase in membrane surface roughness, decrease in membrane fluidity, bilayer thinning at ld domains and disruption of the so domain borders. In terms of structural properties, both enfuvirtide and T-1249 possess distinct functional hydrophobic and amphipathic domains of HIV gp41. While enfuvirtide only yields the tryptophan-rich domain (TRD), T-1249 possesses both TRD and pocket-binding domain (PBD). TRD increases the hydrophobicity of the peptide while PBD enhances the amphipathic characteristics. As such, the enhanced membrane activity of T-1249 may be explained by a synergism between its amphipathic N-terminal segment and its hydrophophic C-terminal. Our findings provide valuable insights on the molecular-level mode of action of HIV-1 fusion inhibitors, unraveling the correlation between their structural properties and membrane interactions as a factor influencing their antiviral activity. Ultimately, this work validates the applicability of a combined AFM and fluorescence approach to evaluate the mechanic and structural properties of supported lipid bilayers upon interaction with membrane-active peptides.The authors thank Roche (Palo Alto, CA) for the kind gift of enfuvirtide and T-1249, and to Pedro Matos (IMM) for the support and helpful discussions. Fundação para a Ciência e Tecnologia–Ministério da Educação e Ciência (Portugal) is acknowledged for the funding (SFRH/BD/39039/2007 and SFRH/BPD/73500/2010 fellowships to H.G.F. and D.G. respectivelyand project grants PTDC/QUI-BIQ/104787/2008, PTDC/QUI-BIQ/112929/2009, VIH/SAU/0047/2011 and REEQ/140/BIO/2005.ElsevierRepositório da Universidade de LisboaFranquelim, Henri G.Gaspar, DianaVeiga, A. SaloméSantos, Nuno C.Castanho, Miguel A. R. B.2014-03-06T11:31:27Z20132013-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/10693engBiochimica et Biophysica Acta 1828 (2013) 1777–17850006-3002metadata only accessinfo:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-03-17T13:06:37Zoai:repositorio.ulisboa.pt:10451/10693Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T02:35:08.357092Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Decoding distinct membrane interactions of HIV-1 fusion inhibitors using a combined atomic force and fluorescence microscopy approach
title Decoding distinct membrane interactions of HIV-1 fusion inhibitors using a combined atomic force and fluorescence microscopy approach
spellingShingle Decoding distinct membrane interactions of HIV-1 fusion inhibitors using a combined atomic force and fluorescence microscopy approach
Franquelim, Henri G.
Fusion inhibitors
Enfuvirtide
T-1249
Atomic force microscopy
Fluorescence microscopy
Supported lipid bilayers
title_short Decoding distinct membrane interactions of HIV-1 fusion inhibitors using a combined atomic force and fluorescence microscopy approach
title_full Decoding distinct membrane interactions of HIV-1 fusion inhibitors using a combined atomic force and fluorescence microscopy approach
title_fullStr Decoding distinct membrane interactions of HIV-1 fusion inhibitors using a combined atomic force and fluorescence microscopy approach
title_full_unstemmed Decoding distinct membrane interactions of HIV-1 fusion inhibitors using a combined atomic force and fluorescence microscopy approach
title_sort Decoding distinct membrane interactions of HIV-1 fusion inhibitors using a combined atomic force and fluorescence microscopy approach
author Franquelim, Henri G.
author_facet Franquelim, Henri G.
Gaspar, Diana
Veiga, A. Salomé
Santos, Nuno C.
Castanho, Miguel A. R. B.
author_role author
author2 Gaspar, Diana
Veiga, A. Salomé
Santos, Nuno C.
Castanho, Miguel A. R. B.
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Franquelim, Henri G.
Gaspar, Diana
Veiga, A. Salomé
Santos, Nuno C.
Castanho, Miguel A. R. B.
dc.subject.por.fl_str_mv Fusion inhibitors
Enfuvirtide
T-1249
Atomic force microscopy
Fluorescence microscopy
Supported lipid bilayers
topic Fusion inhibitors
Enfuvirtide
T-1249
Atomic force microscopy
Fluorescence microscopy
Supported lipid bilayers
description © 2013 Elsevier B.V. All rights reserved.
publishDate 2013
dc.date.none.fl_str_mv 2013
2013-01-01T00:00:00Z
2014-03-06T11:31:27Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/10693
url http://hdl.handle.net/10451/10693
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Biochimica et Biophysica Acta 1828 (2013) 1777–1785
0006-3002
dc.rights.driver.fl_str_mv metadata only access
info:eu-repo/semantics/openAccess
rights_invalid_str_mv metadata only access
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron:RCAAP
instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
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