De Novo Design of Integrin a5ß1 Modulating Proteins for Regenerative Medicine.
Por:
Wang X, Guillem 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 and Baker D
Publicada:
10 jul 2024
Ahead of Print:
10 jul 2024
Resumen:
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.
Open Access
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