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De Novo Design of Integrin α5ß1 Modulating Proteins for Regenerative Medicine.
Wang, Xinru; Guillem-Marti, Jordi; Kumar, Saurav; Lee, David S; Cabrerizo-Aguado, Daniel; Werther, Rachel; Alamo, Kevin Alexander Estrada; Zhao, Yan Ting; Nguyen, Adam; Kopyeva, Irina; Huang, Buwei; Li, Jing; Hao, Yuxin; Li, Xinting; Brizuela-Velasco, Aritza; Murray, Analisa; Gerben, Stacey; Roy, Anindya; DeForest, Cole A; Springer, Timothy; Ruohola-Baker, Hannele; Cooper, Jonathan A; Campbell, Melody G; Manero, Jose Maria; Ginebra, Maria-Pau; Baker, David.
Afiliación
  • Wang X; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Guillem-Marti J; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Kumar S; Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Universitat Politècnica de Catalunya - BarcelonaTech (UPC), Barcelona, Spain.
  • Lee DS; Networking Research Centre of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Institute of Health Carlos III, Madrid, Spain.
  • Cabrerizo-Aguado D; Division of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Werther R; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Alamo KAE; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Zhao YT; Department of Genome Sciences, University of Washington, Seattle, WA, USA.
  • Nguyen A; Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Universitat Politècnica de Catalunya - BarcelonaTech (UPC), Barcelona, Spain.
  • Kopyeva I; Division of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Huang B; Division of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Li J; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Hao Y; Oral Health Sciences, School of Dentistry, University of Washington, Seattle, WA, USA.
  • Li X; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.
  • Brizuela-Velasco A; Division of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Murray A; Graduate Program in Biological Physics, Structure and Design, University of Washington, Seattle, WA, USA.
  • Gerben S; Department of Bioengineering, University of Washington, Seattle, WA, USA.
  • Roy A; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • DeForest CA; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Springer T; Department of Bioengineering, University of Washington, Seattle, WA, USA.
  • Ruohola-Baker H; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
  • Cooper JA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Campbell MG; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
  • Manero JM; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
  • Ginebra MP; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Baker D; Department of Biochemistry, University of Washington, Seattle, WA, USA.
bioRxiv ; 2024 Jul 10.
Article en En | MEDLINE | ID: mdl-38979380
ABSTRACT
Integrin α5ß1 is crucial for cell attachment and migration in development and tissue regeneration, and α5ß1 binding proteins could have considerable utility in regenerative medicine and next-generation therapeutics. We use computational protein design to create de novo α5ß1-specific modulating miniprotein binders, called NeoNectins, that bind to and stabilize the open state of α5ß1. 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos