biostudies-literatureUnknownWang XNIDCR NIH HHSNHLBI NIH HHSNCI NIH HHSNIGMS NIH HHSIntegrin 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.bioRxiv : the preprint server for biology2024.06.21.600123https://www.ebi.ac.uk/biostudies/studies/S-EPMC11230231biostudies-literatureDe Novo Design of Integrin α5β1 Modulating Proteins for Regenerative Medicine.PMC11230231R35 GM147414R01 HL131729P30 CA015704T90 DE021984T32 CA080416R35 GM138036R01 GM109463Guillem-Marti JBaker DSpringer THao YZhao YTKumar SMurray AWang XDeForest CAManero JMHuang BAlamo KAEBrizuela-Velasco ARuohola-Baker HLi JCampbell MGKopyeva IRoy AWerther RLee DSCabrerizo-Aguado DGerben SLi XNguyen ACooper JAGinebra MPfalseDe 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.2024-01-01T00:00:00Z2024 Jul2026-07-05T03:17:37.929Z2025-04-04T22:47:44.68ZS-EPMC112302313897938010.1101/2024.06.21.600123