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

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: (i) is 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. Endowing materials with a custom-designed biological coating is pivotal in nanobiotechnology. Here we present new strategy to control critical aspects, such as protein misorientation, inactivation, detachment or unspecific protein biofouling, for the development of programmable nano–bio interfaces using material science and molecular biology technologies. [Display omitted]