De Novo Design of Integrin a5ß1 Modulating Proteins for Regenerative Medicine.

Integrin a5ß1 is crucial for cell attachment and migration in development and tissue regeneration, and a5ß1 binding proteins could have considerable utility in regenerative medicine and next-generation therapeutics. We use computational protein design to create de novo a5ß1-specific modulating minip...

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Detalhes bibliográficos
Autores: Wang X, Guillem-Marti J, Kumar S, Lee DS, Cabrerizo-Aguado D, Werther R, Alamo KAE, Zhao YT, Nguyen A, Kopyeva I, Huang B, Li J, Hao Y, Li X, Brizuela-Velasco A, Murray A, Gerben S, Roy A, DeForest CA, Springer T, Ruohola-Baker H, Cooper JA, Campbell MG, Manero JM, Ginebra MP, Baker D
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Recursos:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p26543
Acesso em linha:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=26543
Access Level:acceso abierto
Palavra-chave:De novo protein design
RGD
biomaterial
hydrogel
integrin a5ß1
regenerative medicine
titanium
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spelling De Novo Design of Integrin a5ß1 Modulating Proteins for Regenerative Medicine.Wang XGuillem-Marti JKumar SLee DSCabrerizo-Aguado DWerther RAlamo KAEZhao YTNguyen AKopyeva IHuang BLi JHao YLi XBrizuela-Velasco AMurray AGerben SRoy ADeForest CASpringer TRuohola-Baker HCooper JACampbell MGManero JMGinebra MPBaker DDe novo protein designRGDbiomaterialhydrogelintegrin a5ß1regenerative medicinetitaniumIntegrin a5ß1 is crucial for cell attachment and migration in development and tissue regeneration, and a5ß1 binding proteins could have considerable utility in regenerative medicine and next-generation therapeutics. We use computational protein design to create de novo a5ß1-specific modulating miniprotein binders, called NeoNectins, that bind to and stabilize the open state of a5ß1. When immobilized onto titanium surfaces and throughout 3D hydrogels, the NeoNectins outperform native fibronectin and RGD peptide in enhancing cell attachment and spreading, and NeoNectin-grafted titanium implants outperformed fibronectin and RGD-grafted implants in animal models in promoting tissue integration and bone growth. NeoNectins should be broadly applicable for tissue engineering and biomedicine. ONE-SENTENCE SUMMARY: A de novo-designed fibronectin substitute, NeoNectin, is specific for integrin a5ß1 and can be incorporated into biomaterials for regenerative medicine.2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=26543bioRxiv : the preprint server for biologyISSN: 26928205reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p265432026-05-27T12:37:41Z
dc.title.none.fl_str_mv De Novo Design of Integrin a5ß1 Modulating Proteins for Regenerative Medicine.
title De Novo Design of Integrin a5ß1 Modulating Proteins for Regenerative Medicine.
spellingShingle De Novo Design of Integrin a5ß1 Modulating Proteins for Regenerative Medicine.
Wang X
De novo protein design
RGD
biomaterial
hydrogel
integrin a5ß1
regenerative medicine
titanium
title_short De Novo Design of Integrin a5ß1 Modulating Proteins for Regenerative Medicine.
title_full De Novo Design of Integrin a5ß1 Modulating Proteins for Regenerative Medicine.
title_fullStr De Novo Design of Integrin a5ß1 Modulating Proteins for Regenerative Medicine.
title_full_unstemmed De Novo Design of Integrin a5ß1 Modulating Proteins for Regenerative Medicine.
title_sort De Novo Design of Integrin a5ß1 Modulating Proteins for Regenerative Medicine.
dc.creator.none.fl_str_mv Wang X
Guillem-Marti J
Kumar S
Lee DS
Cabrerizo-Aguado D
Werther R
Alamo KAE
Zhao YT
Nguyen A
Kopyeva I
Huang B
Li J
Hao Y
Li X
Brizuela-Velasco A
Murray A
Gerben S
Roy A
DeForest CA
Springer T
Ruohola-Baker H
Cooper JA
Campbell MG
Manero JM
Ginebra MP
Baker D
author Wang X
author_facet Wang X
Guillem-Marti J
Kumar S
Lee DS
Cabrerizo-Aguado D
Werther R
Alamo KAE
Zhao YT
Nguyen A
Kopyeva I
Huang B
Li J
Hao Y
Li X
Brizuela-Velasco A
Murray A
Gerben S
Roy A
DeForest CA
Springer T
Ruohola-Baker H
Cooper JA
Campbell MG
Manero JM
Ginebra MP
Baker D
author_role author
author2 Guillem-Marti J
Kumar S
Lee DS
Cabrerizo-Aguado D
Werther R
Alamo KAE
Zhao YT
Nguyen A
Kopyeva I
Huang B
Li J
Hao Y
Li X
Brizuela-Velasco A
Murray A
Gerben S
Roy A
DeForest CA
Springer T
Ruohola-Baker H
Cooper JA
Campbell MG
Manero JM
Ginebra MP
Baker D
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv De novo protein design
RGD
biomaterial
hydrogel
integrin a5ß1
regenerative medicine
titanium
topic De novo protein design
RGD
biomaterial
hydrogel
integrin a5ß1
regenerative medicine
titanium
description Integrin a5ß1 is crucial for cell attachment and migration in development and tissue regeneration, and a5ß1 binding proteins could have considerable utility in regenerative medicine and next-generation therapeutics. We use computational protein design to create de novo a5ß1-specific modulating miniprotein binders, called NeoNectins, that bind to and stabilize the open state of a5ß1. When immobilized onto titanium surfaces and throughout 3D hydrogels, the NeoNectins outperform native fibronectin and RGD peptide in enhancing cell attachment and spreading, and NeoNectin-grafted titanium implants outperformed fibronectin and RGD-grafted implants in animal models in promoting tissue integration and bone growth. NeoNectins should be broadly applicable for tissue engineering and biomedicine. ONE-SENTENCE SUMMARY: A de novo-designed fibronectin substitute, NeoNectin, is specific for integrin a5ß1 and can be incorporated into biomaterials for regenerative medicine.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=26543
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=26543
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv bioRxiv : the preprint server for biology
ISSN: 26928205
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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