The Interleukin-6 (IL-6) family of cytokines regulates
inflammation
and 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 require
substantial processing time, cost, machinery, and specialist training.
Understanding the fundamental molecular recognition mechanism of cytokines
with synthetic substrates is key to developing new biomedical technologies
such as assays, sensors, and therapeutics that overcome the above
limitations. Herein, we use the corona phase molecular recognition
(CoPhMoRe) approach to engineer new carbon nanotube constructs and
study their binding to the inflammatory cytokines: IL-6, interleukin-11
(IL-11), ciliary neurotrophic factor (CNTF), and leukemia inhibitory
factor (LIF). Library screening identified two polymer-based CoPhMoRe
constructs consisting of single-walled carbon nanotubes complexed
with p(AA68-rand-BA16-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 μg/mL, respectively, compared to
that of the natural IL-6 receptor at ∼0.32 ng/mL. In addition,
the MK2 constructs showed a nonmonotonic response function upon binding
with IL-6. Comparative binding experiments suggest that both constructs
appear to recognize the axially aligned α-helical structures
present in the Interleukin-6 family. The findings from this study
elucidate how nanoparticle interfaces, such as those produced by CoPhMoRe,
can be designed to lock onto specific protein features. We find that
the α-helical structure of the IL-6 family of cytokines can
enable facile molecular recognition, opening the door to new types
of label-free, low-cost sensing technologies.