Corona Phase Molecular Recognition of the Interleukin-6 (IL-6) Family of Cytokines Using nIR Fluorescent Single-Walled Carbon Nanotubes

The Interleukin-6 (IL-6) family of cytokines regulatesinflammationand plays important roles in numerous biochemical pathways. Typically,cytokine levels are measured using enzyme-linked immunosorbent assay(ELISA) or western blot. However, these techniques usually requiresubstantial processing time, cost, machinery, and specialist training.Understanding the fundamental molecular recognition mechanism of cytokineswith synthetic substrates is key to developing new biomedical technologiessuch as assays, sensors, and therapeutics that overcome the abovelimitations. Herein, we use the corona phase molecular recognition(CoPhMoRe) approach to engineer new carbon nanotube constructs andstudy their binding to the inflammatory cytokines: IL-6, interleukin-11(IL-11), ciliary neurotrophic factor (CNTF), and leukemia inhibitoryfactor (LIF). Library screening identified two polymer-based CoPhMoReconstructs consisting of single-walled carbon nanotubes complexedwith p-(AA(68)-rand-BA(16)-rand-CD16) polymer (MK2) or p-(SS80-rand-BS20) polymer (P14) corona phases.The resulting dissociation constants (K (D)) were 8.38 ng/mL and 16.7 mu g/mL, respectively, compared tothat of the natural IL-6 receptor at similar to 0.32 ng/mL. In addition,the MK2 constructs showed a nonmonotonic response function upon bindingwith IL-6. Comparative binding experiments suggest that both constructsappear to recognize the axially aligned alpha-helical structurespresent in the Interleukin-6 family. The findings from this studyelucidate how nanoparticle interfaces, such as those produced by CoPhMoRe,can be designed to lock onto specific protein features. We find thatthe alpha-helical structure of the IL-6 family of cytokines canenable facile molecular recognition, opening the door to new typesof label-free, low-cost sensing technologies.