Designer Proteins Boost the Performance of Titanium Implants

A new study led by  Xinru Wang, PhD and Jordi Guillem-Marti at the Baker Lab introduces NeoNectins. The study is titled: De Novo Design of Integrin α5β1 Modulating Proteins to Enhance Biomaterial Properties.

Collaborating labs: Cole DeForest, Timothy Springer, Hannele Ruohola-Baker, Jonathan Cooper, Melody Campbell, Jose Maria Manero, and Maria Pau Ginebra

Background

Integrin α5β1 is a key receptor that mediates cell attachment and migration, critical processes in development, wound healing, and bone regeneration. Traditional methods use full-length fibronectin (FN) or short RGD peptides to activate this integrin. However, FN is hard to mass-produce and prone to degradation, while RGD peptides bind weakly and non-specifically to multiple integrins, not just α5β1.

What are NeoNectins?

The authors introduce NeoNectins: custom-designed, de novo miniproteins crafted via computational design to specifically target and activate α5β1. Built on a stable ferredoxin-like scaffold, they strategically graft an RGD motif plus surrounding loops to lock integrin α5β1 into its active, “open” state. This strategy tackles integrin specificity at a molecular level.

Results

• Affinity & specificity: The top candidate (NN‑C1) binds α5β1 with a KD of ~1.9 nM on cells, outperforming fibronectin (KD ~612 nM) and RGD peptides (~150 µM) by orders of magnitude.
  
• Structural validation: Cryo-EM reveals NeoNectin stabilizes the integrin in its extended open conformation (~85–90% of particles), matching native ligand behavior.
  
• Cell behavior: Surfaces functionalized with NeoNectin (on titanium or within 3D hydrogels) promote faster and more robust cell spreading, focal adhesion formation, and signaling than surfaces coated with FN or RGD.
  
• In vivo integration: In animal models, titanium implants coated with NeoNectins supported superior tissue integration and bone growth, outperforming implants grafted with FN or RGD.
  

How does it come into play?

NeoNectins combine stability, specificity, and potency in a small, manufacturable package. They offer clear advantages for tissue engineering and biomedicine, enabling improved implant coatings and engineered hydrogels. They can help the body respond to surgical implants, healing gels, and other biomaterials. As the authors conclude, these designer proteins “should be broadly applicable for tissue engineering and biomedicine,” marking a significant advance over traditional ECM components.Bottom line: NeoNectins represent a leap forward, delivering nanomolar binding strength, targeted activation of the integrin α5β1, and superior functional outcomes in cells and living systems; all wrapped into compact, engineerable proteins.