Xinru Wang, Jordi Guillem-Marti, Saurav Kumar, David S Lee, Daniel Cabrerizo-Aguado, Rachel Werther, Kevin Alexander Estrada Alamo, Yan Ting Zhao, Adam Nguyen, Irina Kopyeva, Buwei Huang, Jing Li, Yuxin Hao, Xinting Li, Aritza Brizuela-Velasco, Analisa Murray, Stacey Gerben, Anindya Roy, Cole A DeForest, Timothy Springer, Hannele Ruohola-Baker, Jonathan A Cooper, Melody G Campbell, Jose Maria Manero, Maria-Pau Ginebra, David Baker
{"title":"De Novo Design of Integrin α5β1 Modulating Proteins to Enhance Biomaterial Properties.","authors":"Xinru Wang, Jordi Guillem-Marti, Saurav Kumar, David S Lee, Daniel Cabrerizo-Aguado, Rachel Werther, Kevin Alexander Estrada Alamo, Yan Ting Zhao, Adam Nguyen, Irina Kopyeva, Buwei Huang, Jing Li, Yuxin Hao, Xinting Li, Aritza Brizuela-Velasco, Analisa Murray, Stacey Gerben, Anindya Roy, Cole A DeForest, Timothy Springer, Hannele Ruohola-Baker, Jonathan A Cooper, Melody G Campbell, Jose Maria Manero, Maria-Pau Ginebra, David Baker","doi":"10.1002/adma.202500872","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":114,"journal":{"name":"Advanced Materials","volume":" ","pages":"e2500872"},"PeriodicalIF":27.4000,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced Materials","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1002/adma.202500872","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍：
Advanced Materials, one of the world's most prestigious journals and the foundation of the Advanced portfolio, is the home of choice for best-in-class materials science for more than 30 years. Following this fast-growing and interdisciplinary field, we are considering and publishing the most important discoveries on any and all materials from materials scientists, chemists, physicists, engineers as well as health and life scientists and bringing you the latest results and trends in modern materials-related research every week.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
