De Novo Design of Integrin a5ß1 Modulating Proteins to Enhance Biomaterial Properties.
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:
1 jun 2025
Ahead of Print:
9 jun 2025
Resumen:
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.
Filiaciones:
Wang X:
Department of Biochemistry, University of Washington, Seattle, WA, USA
Institute for Protein Design, University of Washington, Seattle, WA, USA
Guillem J:
Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Universitat Politècnica de Catalunya - BarcelonaTech (UPC), Barcelona, Spain
Networking Research Centre of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Institute of Health Carlos III, Madrid, Spain
Kumar S:
Division of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA
LILA Biologics, Seattle, WA, USA
Lee DS:
Department of Biochemistry, University of Washington, Seattle, WA, USA
Institute for Protein Design, University of Washington, Seattle, WA, USA
Department of Genome Sciences, University of Washington, Seattle, WA, USA
Cabrerizo-Aguado D:
Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Universitat Politècnica de Catalunya - BarcelonaTech (UPC), Barcelona, Spain
Werther R:
Division of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA
Alamo KAE:
Division of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA
Zhao YT:
Department of Biochemistry, University of Washington, Seattle, WA, USA
Oral Health Sciences, School of Dentistry, University of Washington, Seattle, WA, USA
Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA
Nguyen A:
Division of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA
Graduate Program in Biological Physics, Structure and Design, University of Washington, Seattle, WA, USA
Kopyeva I:
Department of Bioengineering, University of Washington, Seattle, WA, USA
Huang B:
Department of Biochemistry, University of Washington, Seattle, WA, USA
Institute for Protein Design, University of Washington, Seattle, WA, USA
Department of Bioengineering, University of Washington, Seattle, WA, USA
Li J:
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, 02115, USA
Department of Pediatrics, Harvard Medical School, Boston, MA, 02115, USA
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA
Hao Y:
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, 02115, USA
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA
Li X:
Department of Biochemistry, University of Washington, Seattle, WA, USA
Institute for Protein Design, University of Washington, Seattle, WA, USA
Brizuela-Velasco A:
DENS-ia Research Group, Faculty of Health Sciences, Miguel de Cervantes European University, Valladolid, Spain
Murray A:
Department of Biochemistry, University of Washington, Seattle, WA, USA
Institute for Protein Design, University of Washington, Seattle, WA, USA
Gerben S:
Department of Biochemistry, University of Washington, Seattle, WA, USA
Institute for Protein Design, University of Washington, Seattle, WA, USA
Roy A:
Department of Biochemistry, University of Washington, Seattle, WA, USA
Institute for Protein Design, University of Washington, Seattle, WA, USA
DeForest CA:
Institute for Protein Design, University of Washington, Seattle, WA, USA
Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA
Department of Bioengineering, University of Washington, Seattle, WA, USA
Department of Chemical Engineering, University of Washington, Seattle, WA, USA
Department of Chemistry, University of Washington, Seattle, WA, USA
Molecular Engineering & Sciences Institute, University of Washington, Seattle, WA, USA
Springer T:
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, 02115, USA
Department of Pediatrics, Harvard Medical School, Boston, MA, 02115, USA
Ruohola-Baker H:
Department of Biochemistry, University of Washington, Seattle, WA, USA
Department of Genome Sciences, University of Washington, Seattle, WA, USA
Oral Health Sciences, School of Dentistry, University of Washington, Seattle, WA, USA
Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA
Department of Bioengineering, University of Washington, Seattle, WA, USA
Cooper JA:
Division of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA
Campbell MG:
Division of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA
Manero JM:
Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Universitat Politècnica de Catalunya - BarcelonaTech (UPC), Barcelona, Spain
Networking Research Centre of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Institute of Health Carlos III, Madrid, Spain
Ginebra MP:
Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Universitat Politècnica de Catalunya - BarcelonaTech (UPC), Barcelona, Spain
Networking Research Centre of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Institute of Health Carlos III, Madrid, Spain
Institute for Bioengineering of Catalonia, Barcelona Institute of Science and Technology, Barcelona, Spain
Baker D:
Department of Biochemistry, University of Washington, Seattle, WA, USA
Institute for Protein Design, University of Washington, Seattle, WA, USA
Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA
Open Access
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