Protein-targeted corona phase molecular recognition

TLDR

Corona phase molecular recognition (CoPhMoRe) employs a heteropolymer adsorbed on a nanoparticle surface to detect specific analytes, but its application to macromolecular targets such as proteins has not yet been explored. The study aims to develop a CoPhMoRe screening variant using single‑walled carbon nanotubes to identify a corona phase that selectively recognizes fibrinogen among human blood proteins. The authors adapted the screening protocol with SWCNTs and screened a panel of human blood proteins, revealing a specific corona phase that binds fibrinogen with high selectivity. Binding of fibrinogen to the identified corona phase quenches SWCNT fluorescence by over 80 % at saturation, with sequential quenching of three nodules confirmed by sub‑domain studies and kinetics, and the interaction persists in serum at physiological fibrinogen levels, demonstrating a promising synthetic antibody analogue for clinical use.

Abstract

Corona phase molecular recognition (CoPhMoRe) uses a heteropolymer adsorbed onto and templated by a nanoparticle surface to recognize a specific target analyte. This method has not yet been extended to macromolecular analytes, including proteins. Herein we develop a variant of a CoPhMoRe screening procedure of single-walled carbon nanotubes (SWCNT) and use it against a panel of human blood proteins, revealing a specific corona phase that recognizes fibrinogen with high selectivity. In response to fibrinogen binding, SWCNT fluorescence decreases by >80% at saturation. Sequential binding of the three fibrinogen nodules is suggested by selective fluorescence quenching by isolated sub-domains and validated by the quenching kinetics. The fibrinogen recognition also occurs in serum environment, at the clinically relevant fibrinogen concentrations in the human blood. These results open new avenues for synthetic, non-biological antibody analogues that recognize biological macromolecules, and hold great promise for medical and clinical applications.