De Novo Design of Integrin α5β1 Modulating Proteins to Enhance Biomaterial Properties
Abstract
Abstract Integrin α5β1 is crucial for cell attachment and migration in development and tissue regeneration, and α5β1 binding proteins can 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 (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.
Article Details
Authors (26)
Xinru Wang
Jordi Guillem‐Marti
Biomaterials, Biomechanics and Tissue Engineering Group Department of Materials Science and Engineering Universitat Politècnica de Catalunya – BarcelonaTech (UPC) Barcelona Spain
Saurav Kumar
David S. Lee
Daniel Cabrerizo‐Aguado
Biomaterials, Biomechanics and Tissue Engineering Group Department of Materials Science and Engineering Universitat Politècnica de Catalunya – BarcelonaTech (UPC) Barcelona Spain
Rachel Werther
Division of Basic Sciences Fred Hutchinson Cancer Center Seattle WA USA
Kevin Alexander Estrada Alamo
Division of Basic Sciences Fred Hutchinson Cancer Center Seattle WA USA
Yan Ting Zhao
Department of Biochemistry University of Washington Seattle WA USA
Adam Nguyen
Division of Basic Sciences Fred Hutchinson Cancer Center Seattle WA USA
Irina Kopyeva
Department of Bioengineering University of Washington Seattle WA USA
Buwei Huang
Jing Li
Yuxin Hao
Xinting Li
Aritza Brizuela‐Velasco
DENS‐ia Research Group Faculty of Health Sciences Miguel de Cervantes European University Valladolid Spain
Analisa Murray
Stacey Gerben
Department of Biochemistry University of Washington Seattle WA USA
Anindya Roy
Department of Biochemistry University of Washington Seattle WA USA
Cole A. DeForest
Department of Chemical Engineering, University of Washington
Timothy Springer
Program in Cellular and Molecular Medicine Boston Children's Hospital Boston MA 02115 USA
Hannele Ruohola‐Baker
Department of Biochemistry University of Washington Seattle WA USA
Jonathan A. Cooper
Division of Basic Sciences Fred Hutchinson Cancer Center Seattle WA USA
Melody G. Campbell
Division of Basic Sciences Fred Hutchinson Cancer Center Seattle WA USA
Jose Maria Manero
Biomaterials, Biomechanics and Tissue Engineering Group Department of Materials Science and Engineering Universitat Politècnica de Catalunya – BarcelonaTech (UPC) Barcelona Spain
Maria‐Pau Ginebra
Biomaterials, Biomechanics and Tissue Engineering Group Department of Materials Science and Engineering Universitat Politècnica de Catalunya – BarcelonaTech (UPC) Barcelona Spain
David Baker