A cooperative transition from the semi-flexible to the flexible regime of polymer elasticity: Mitoxantrone-induced DNA condensation
Autor(a) principal: | |
---|---|
Data de Publicação: | 2018 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | LOCUS Repositório Institucional da UFV |
Texto Completo: | https://doi.org/10.1016/j.bbagen.2018.01.019 http://www.locus.ufv.br/handle/123456789/18718 |
Resumo: | We report a high cooperative transition from the semi-flexible to the flexible regime of polymer elasticity during the interaction of the DNA molecule with the chemotherapeutic drug Mitoxantrone (MTX). By using single molecule force spectroscopy, we show that the force-extension curves of the DNA-MTX complexes deviate from the typical worm-like chain behavior as the MTX concentration in the sample increases, becoming straight lines for sufficiently high drug concentrations. The behavior of the radius of gyration of the complexes as a function of the bound MTX concentration was used to quantitatively investigate the cooperativity of the condensation process. The present methodology can be promptly applied to other ligands that condense the DNA molecule upon binding, opening new possibilities in the investigation of this type of process and, more generally, in the investigation of phase transitions in polymer physics. |
id |
UFV_3cbcff890ec9e62c231d3e0946349014 |
---|---|
oai_identifier_str |
oai:locus.ufv.br:123456789/18718 |
network_acronym_str |
UFV |
network_name_str |
LOCUS Repositório Institucional da UFV |
repository_id_str |
2145 |
spelling |
Lima, C.H.M.Almeida, G.O.Rocha, M.S.2018-04-16T15:48:50Z2018-04-16T15:48:50Z2018-01-300304-4165https://doi.org/10.1016/j.bbagen.2018.01.019http://www.locus.ufv.br/handle/123456789/18718We report a high cooperative transition from the semi-flexible to the flexible regime of polymer elasticity during the interaction of the DNA molecule with the chemotherapeutic drug Mitoxantrone (MTX). By using single molecule force spectroscopy, we show that the force-extension curves of the DNA-MTX complexes deviate from the typical worm-like chain behavior as the MTX concentration in the sample increases, becoming straight lines for sufficiently high drug concentrations. The behavior of the radius of gyration of the complexes as a function of the bound MTX concentration was used to quantitatively investigate the cooperativity of the condensation process. The present methodology can be promptly applied to other ligands that condense the DNA molecule upon binding, opening new possibilities in the investigation of this type of process and, more generally, in the investigation of phase transitions in polymer physics.engBiochimica et Biophysica Acta (BBA) - General SubjectsVolume 1862, Issue 5, Pages 1107-1114, May 2018DNA condensationMitoxantronePolymer elasticityForce spectroscopyA cooperative transition from the semi-flexible to the flexible regime of polymer elasticity: Mitoxantrone-induced DNA condensationinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfinfo:eu-repo/semantics/openAccessreponame:LOCUS Repositório Institucional da UFVinstname:Universidade Federal de Viçosa (UFV)instacron:UFVORIGINALartigo.pdfartigo.pdfTexto completoapplication/pdf1746294https://locus.ufv.br//bitstream/123456789/18718/1/artigo.pdf17eab5d259e0648ed564ed1365284158MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://locus.ufv.br//bitstream/123456789/18718/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52THUMBNAILartigo.pdf.jpgartigo.pdf.jpgIM Thumbnailimage/jpeg6110https://locus.ufv.br//bitstream/123456789/18718/3/artigo.pdf.jpgc4c5cc0b94a5b218bc9d8aa0ecdf1dc5MD53123456789/187182018-04-16 23:00:40.296oai:locus.ufv.br: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Repositório InstitucionalPUBhttps://www.locus.ufv.br/oai/requestfabiojreis@ufv.bropendoar:21452018-04-17T02:00:40LOCUS Repositório Institucional da UFV - Universidade Federal de Viçosa (UFV)false |
dc.title.en.fl_str_mv |
A cooperative transition from the semi-flexible to the flexible regime of polymer elasticity: Mitoxantrone-induced DNA condensation |
title |
A cooperative transition from the semi-flexible to the flexible regime of polymer elasticity: Mitoxantrone-induced DNA condensation |
spellingShingle |
A cooperative transition from the semi-flexible to the flexible regime of polymer elasticity: Mitoxantrone-induced DNA condensation Lima, C.H.M. DNA condensation Mitoxantrone Polymer elasticity Force spectroscopy |
title_short |
A cooperative transition from the semi-flexible to the flexible regime of polymer elasticity: Mitoxantrone-induced DNA condensation |
title_full |
A cooperative transition from the semi-flexible to the flexible regime of polymer elasticity: Mitoxantrone-induced DNA condensation |
title_fullStr |
A cooperative transition from the semi-flexible to the flexible regime of polymer elasticity: Mitoxantrone-induced DNA condensation |
title_full_unstemmed |
A cooperative transition from the semi-flexible to the flexible regime of polymer elasticity: Mitoxantrone-induced DNA condensation |
title_sort |
A cooperative transition from the semi-flexible to the flexible regime of polymer elasticity: Mitoxantrone-induced DNA condensation |
author |
Lima, C.H.M. |
author_facet |
Lima, C.H.M. Almeida, G.O. Rocha, M.S. |
author_role |
author |
author2 |
Almeida, G.O. Rocha, M.S. |
author2_role |
author author |
dc.contributor.author.fl_str_mv |
Lima, C.H.M. Almeida, G.O. Rocha, M.S. |
dc.subject.pt-BR.fl_str_mv |
DNA condensation Mitoxantrone Polymer elasticity Force spectroscopy |
topic |
DNA condensation Mitoxantrone Polymer elasticity Force spectroscopy |
description |
We report a high cooperative transition from the semi-flexible to the flexible regime of polymer elasticity during the interaction of the DNA molecule with the chemotherapeutic drug Mitoxantrone (MTX). By using single molecule force spectroscopy, we show that the force-extension curves of the DNA-MTX complexes deviate from the typical worm-like chain behavior as the MTX concentration in the sample increases, becoming straight lines for sufficiently high drug concentrations. The behavior of the radius of gyration of the complexes as a function of the bound MTX concentration was used to quantitatively investigate the cooperativity of the condensation process. The present methodology can be promptly applied to other ligands that condense the DNA molecule upon binding, opening new possibilities in the investigation of this type of process and, more generally, in the investigation of phase transitions in polymer physics. |
publishDate |
2018 |
dc.date.accessioned.fl_str_mv |
2018-04-16T15:48:50Z |
dc.date.available.fl_str_mv |
2018-04-16T15:48:50Z |
dc.date.issued.fl_str_mv |
2018-01-30 |
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 |
https://doi.org/10.1016/j.bbagen.2018.01.019 http://www.locus.ufv.br/handle/123456789/18718 |
dc.identifier.issn.none.fl_str_mv |
0304-4165 |
identifier_str_mv |
0304-4165 |
url |
https://doi.org/10.1016/j.bbagen.2018.01.019 http://www.locus.ufv.br/handle/123456789/18718 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartofseries.pt-BR.fl_str_mv |
Volume 1862, Issue 5, Pages 1107-1114, May 2018 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Biochimica et Biophysica Acta (BBA) - General Subjects |
publisher.none.fl_str_mv |
Biochimica et Biophysica Acta (BBA) - General Subjects |
dc.source.none.fl_str_mv |
reponame:LOCUS Repositório Institucional da UFV instname:Universidade Federal de Viçosa (UFV) instacron:UFV |
instname_str |
Universidade Federal de Viçosa (UFV) |
instacron_str |
UFV |
institution |
UFV |
reponame_str |
LOCUS Repositório Institucional da UFV |
collection |
LOCUS Repositório Institucional da UFV |
bitstream.url.fl_str_mv |
https://locus.ufv.br//bitstream/123456789/18718/1/artigo.pdf https://locus.ufv.br//bitstream/123456789/18718/2/license.txt https://locus.ufv.br//bitstream/123456789/18718/3/artigo.pdf.jpg |
bitstream.checksum.fl_str_mv |
17eab5d259e0648ed564ed1365284158 8a4605be74aa9ea9d79846c1fba20a33 c4c5cc0b94a5b218bc9d8aa0ecdf1dc5 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
LOCUS Repositório Institucional da UFV - Universidade Federal de Viçosa (UFV) |
repository.mail.fl_str_mv |
fabiojreis@ufv.br |
_version_ |
1801213007419670528 |