A custom-made functionalization method to control the biological identity of nanomaterials

Abstract Here we propose a one-step strategy to endow nanomaterials with a custom-designed bio-identity. This study designs a universal `nanomaterial binding domain´ that can be genetically attached to any protein ensuring precise and spontaneous protein orientation. We demonstrate how, despite the simplicity of the method, the bioconjugation achieved is: (i) highly efficient, even in the presence of competing proteins, (ii) is stable at extreme physiological conditions (pH ranges 5.2–9.0; NaCl concentrations 0–1 M); (iii) prevents unwanted protein biofouling days after incubation in biologically-relevant conditions; and finally, (iv) avoids nanoparticle interaction with promiscuous unspecific receptors. In summary, this protein biocoating technique, applicable to a wide array of nano-designs, integrates material science and molecular biology procedures to create hybrid nanodevices with well-defined surfaces and predictable biological behaviors, opening a chapter in precision nanodiagnostics, nanosensing or nanotherapeutic applications.