De novo design of integrin a5ß1 modulating proteins to enhance biomaterial properties

Wang, Xinru; Guillem Martí, Jordi|||0000-0003-0307-2221; Kumar, Saurav|||0000-0002-0992-589X; Lee, David; Cabrerizo Aguado, Daniel|||0009-0006-2410-6936; Werther, Rachel|||0000-0002-3058-1550; Estrada Alamo, Kevin Alexander|||0000-0002-3829-357X; Zhao, Yan Ting|||0000-0001-9230-7066; Nguyen, Adam; Kopyeva, Irina; Huang, Buwei; Li, Jing; Hao, Yuxin; Li, Xinting; Brizuela Velasco, Aritza; Murray, Analisa; Gerben, Stacey; Roy, Anindya; DeForest, Cole A.; Springer, Timothy; Ruohola-Baker, Hannele; Cooper, Jonathan; Campbell, Melody; Manero Planella, José María|||0000-0002-1673-4389; Ginebra Molins, Maria Pau|||0000-0002-4700-5621; Baker, David

De novo design of integrin a5ß1 modulating proteins to enhance biomaterial properties

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

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Authors:	Wang, Xinru, Guillem Martí, Jordi\|\|\|0000-0003-0307-2221, Kumar, Saurav\|\|\|0000-0002-0992-589X, Lee, David, Cabrerizo Aguado, Daniel\|\|\|0009-0006-2410-6936, Werther, Rachel\|\|\|0000-0002-3058-1550, Estrada Alamo, Kevin Alexander\|\|\|0000-0002-3829-357X, Zhao, Yan Ting\|\|\|0000-0001-9230-7066, Nguyen, Adam, Kopyeva, Irina, Huang, Buwei, Li, Jing, Hao, Yuxin, Li, Xinting, Brizuela Velasco, Aritza, Murray, Analisa, Gerben, Stacey, Roy, Anindya, DeForest, Cole A., Springer, Timothy, Ruohola-Baker, Hannele, Cooper, Jonathan, Campbell, Melody, Manero Planella, José María\|\|\|0000-0002-1673-4389, Ginebra Molins, Maria Pau\|\|\|0000-0002-4700-5621, Baker, David
Format:	article
Publication Date:	2025
Country:	España
Institution:	Universitat Politècnica de Catalunya (UPC)
Repository:	UPCommons. Portal del coneixement obert de la UPC
Language:	English
OAI Identifier:	oai:upcommons.upc.edu:2117/443439
Online Access:	https://hdl.handle.net/2117/443439 https://dx.doi.org/10.1002/adma.202500872
Access Level:	Open access
Keyword:	Biomaterial De novo protein design Hydrogel Integrin a5ß1 Regenerative medicine RGD Titanium Àrees temàtiques de la UPC::Enginyeria biomèdica

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spelling	De novo design of integrin a5ß1 modulating proteins to enhance biomaterial propertiesWang, XinruGuillem Martí, Jordi\|\|\|0000-0003-0307-2221Kumar, Saurav\|\|\|0000-0002-0992-589XLee, DavidCabrerizo Aguado, Daniel\|\|\|0009-0006-2410-6936Werther, Rachel\|\|\|0000-0002-3058-1550Estrada Alamo, Kevin Alexander\|\|\|0000-0002-3829-357XZhao, Yan Ting\|\|\|0000-0001-9230-7066Nguyen, AdamKopyeva, IrinaHuang, BuweiLi, JingHao, YuxinLi, XintingBrizuela Velasco, AritzaMurray, AnalisaGerben, StaceyRoy, AnindyaDeForest, Cole A.Springer, TimothyRuohola-Baker, HanneleCooper, JonathanCampbell, MelodyManero Planella, José María\|\|\|0000-0002-1673-4389Ginebra Molins, Maria Pau\|\|\|0000-0002-4700-5621Baker, DavidBiomaterialDe novo protein designHydrogelIntegrin a5ß1Regenerative medicineRGDTitaniumÀrees temàtiques de la UPC::Enginyeria biomèdicaIntegrin a5ß1 is crucial for cell attachment and migration in development and tissue regeneration, and a5ß1 binding proteins can 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 (FN) and RGD peptides in enhancing cell attachment and spreading, and NeoNectin-grafted titanium implants outperformed FN- and RGD-grafted implants in animal models in promoting tissue integration and bone growth. NeoNectins should be broadly applicable for tissue engineering and biomedicine.Peer Reviewed20252025-06-0920252025-10-10journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttps://hdl.handle.net/2117/443439https://dx.doi.org/10.1002/adma.202500872reponame:UPCommons. Portal del coneixement obert de la UPCinstname:Universitat Politècnica de Catalunya (UPC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:upcommons.upc.edu:2117/4434392026-05-27T15:37:01Z
dc.title.none.fl_str_mv	De novo design of integrin a5ß1 modulating proteins to enhance biomaterial properties
title	De novo design of integrin a5ß1 modulating proteins to enhance biomaterial properties
spellingShingle	De novo design of integrin a5ß1 modulating proteins to enhance biomaterial properties Wang, Xinru Biomaterial De novo protein design Hydrogel Integrin a5ß1 Regenerative medicine RGD Titanium Àrees temàtiques de la UPC::Enginyeria biomèdica
title_short	De novo design of integrin a5ß1 modulating proteins to enhance biomaterial properties
title_full	De novo design of integrin a5ß1 modulating proteins to enhance biomaterial properties
title_fullStr	De novo design of integrin a5ß1 modulating proteins to enhance biomaterial properties
title_full_unstemmed	De novo design of integrin a5ß1 modulating proteins to enhance biomaterial properties
title_sort	De novo design of integrin a5ß1 modulating proteins to enhance biomaterial properties
dc.creator.none.fl_str_mv	Wang, Xinru Guillem Martí, Jordi\|\|\|0000-0003-0307-2221 Kumar, Saurav\|\|\|0000-0002-0992-589X Lee, David Cabrerizo Aguado, Daniel\|\|\|0009-0006-2410-6936 Werther, Rachel\|\|\|0000-0002-3058-1550 Estrada Alamo, Kevin Alexander\|\|\|0000-0002-3829-357X Zhao, Yan Ting\|\|\|0000-0001-9230-7066 Nguyen, Adam Kopyeva, Irina Huang, Buwei Li, Jing Hao, Yuxin Li, Xinting Brizuela Velasco, Aritza Murray, Analisa Gerben, Stacey Roy, Anindya DeForest, Cole A. Springer, Timothy Ruohola-Baker, Hannele Cooper, Jonathan Campbell, Melody Manero Planella, José María\|\|\|0000-0002-1673-4389 Ginebra Molins, Maria Pau\|\|\|0000-0002-4700-5621 Baker, David
author	Wang, Xinru
author_facet	Wang, Xinru Guillem Martí, Jordi\|\|\|0000-0003-0307-2221 Kumar, Saurav\|\|\|0000-0002-0992-589X Lee, David Cabrerizo Aguado, Daniel\|\|\|0009-0006-2410-6936 Werther, Rachel\|\|\|0000-0002-3058-1550 Estrada Alamo, Kevin Alexander\|\|\|0000-0002-3829-357X Zhao, Yan Ting\|\|\|0000-0001-9230-7066 Nguyen, Adam Kopyeva, Irina Huang, Buwei Li, Jing Hao, Yuxin Li, Xinting Brizuela Velasco, Aritza Murray, Analisa Gerben, Stacey Roy, Anindya DeForest, Cole A. Springer, Timothy Ruohola-Baker, Hannele Cooper, Jonathan Campbell, Melody Manero Planella, José María\|\|\|0000-0002-1673-4389 Ginebra Molins, Maria Pau\|\|\|0000-0002-4700-5621 Baker, David
author_role	author
author2	Guillem Martí, Jordi\|\|\|0000-0003-0307-2221 Kumar, Saurav\|\|\|0000-0002-0992-589X Lee, David Cabrerizo Aguado, Daniel\|\|\|0009-0006-2410-6936 Werther, Rachel\|\|\|0000-0002-3058-1550 Estrada Alamo, Kevin Alexander\|\|\|0000-0002-3829-357X Zhao, Yan Ting\|\|\|0000-0001-9230-7066 Nguyen, Adam Kopyeva, Irina Huang, Buwei Li, Jing Hao, Yuxin Li, Xinting Brizuela Velasco, Aritza Murray, Analisa Gerben, Stacey Roy, Anindya DeForest, Cole A. Springer, Timothy Ruohola-Baker, Hannele Cooper, Jonathan Campbell, Melody Manero Planella, José María\|\|\|0000-0002-1673-4389 Ginebra Molins, Maria Pau\|\|\|0000-0002-4700-5621 Baker, David
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	Biomaterial De novo protein design Hydrogel Integrin a5ß1 Regenerative medicine RGD Titanium Àrees temàtiques de la UPC::Enginyeria biomèdica
topic	Biomaterial De novo protein design Hydrogel Integrin a5ß1 Regenerative medicine RGD Titanium Àrees temàtiques de la UPC::Enginyeria biomèdica
description	Integrin a5ß1 is crucial for cell attachment and migration in development and tissue regeneration, and a5ß1 binding proteins can 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 (FN) and RGD peptides in enhancing cell attachment and spreading, and NeoNectin-grafted titanium implants outperformed FN- and RGD-grafted implants in animal models in promoting tissue integration and bone growth. NeoNectins should be broadly applicable for tissue engineering and biomedicine.
publishDate	2025
dc.date.none.fl_str_mv	2025 2025-06-09 2025 2025-10-10
dc.type.none.fl_str_mv	journal article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://hdl.handle.net/2117/443439 https://dx.doi.org/10.1002/adma.202500872
url	https://hdl.handle.net/2117/443439 https://dx.doi.org/10.1002/adma.202500872
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf application/pdf
dc.source.none.fl_str_mv	reponame:UPCommons. Portal del coneixement obert de la UPC instname:Universitat Politècnica de Catalunya (UPC)
instname_str	Universitat Politècnica de Catalunya (UPC)
reponame_str	UPCommons. Portal del coneixement obert de la UPC
collection	UPCommons. Portal del coneixement obert de la UPC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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De novo design of integrin a5ß1 modulating proteins to enhance biomaterial properties

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