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 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución: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:p28729
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=28729
Access Level:acceso abierto
Palabra clave:RGD
biomaterial
de novo protein design
hydrogel
integrin a5ß1
regenerative medicine
titanium
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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