De Novo Design of Integrin α5β1 Modulating Proteins for Regenerative Medicine.

Integrin α5β1 is crucial for cell attachment and migration in development and tissue regeneration, and α5β1 binding proteins could have considerable utility in regenerative medicine and next-generation therapeutics. We use computational protein design to create de novo α5β1-specific modulating miniprotein binders, called NeoNectins, that bind to and stabilize the open state of α5β1. 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.
Competing Interests: Conflict of interest X.W., J.G-M, B.H., and D.B. are co-inventors on an International patent (Serial 63/570,567) filed by the University of Washington covering molecules and their uses described in this manuscript. A.R., X.W., and D.B. are co-founders of Lila Biologics and own stock or stock options in the company. All other authors declare no competing interests.