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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Detalles Bibliográficos
Autores: 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
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universitat Politècnica de Catalunya (UPC)
Repositorio:UPCommons. Portal del coneixement obert de la UPC
Idioma:inglés
OAI Identifier:oai:upcommons.upc.edu:2117/443439
Acceso en línea:https://hdl.handle.net/2117/443439
https://dx.doi.org/10.1002/adma.202500872
Access Level:acceso abierto
Palabra clave:Biomaterial
De novo protein design
Hydrogel
Integrin a5ß1
Regenerative medicine
RGD
Titanium
Àrees temàtiques de la UPC::Enginyeria biomèdica
Descripción
Sumario: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.

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