Conformationally Adaptive Peptide Nanolayers for Metal Ions Biosensing

Cu²⁺ and Zn²⁺ metal ions play a significant role in important biological processes. Deviations in ion concentration from defined values are associated with various diseases, and hence, can be used as a diagnostic target. The typical monitoring of ion concentration has limitations in portability, cost, and ease of use.

Herein we present a label-free, highly sensitive electrochemical biosensor based on peptides with inherent affinity to Cu²⁺ and Zn²⁺ metal ions. The suggested sensing mechanism is based on direct chemisorption of a peptide layer on gold electrode and further exposure of the modified electrode to Cu²⁺ and Zn²⁺ ions. Ion chelation results in conformational changes in the peptide layer, and thereby influences the redox species transfer to the electrode surface.

We present two peptides for sensing of metal ions. GGH tri-peptide labeled with Lipoic acid adsorbed directly on the gold surface. The chelation process with Cu²⁺ ions produces a loop of the peptide tail. On the other hand, Oxytocin is a native neuropeptide which has different binding sites to Cu²⁺ and Zn²⁺ ions. Adsorption to gold surface attributed with the opening of disulfide bond that allows ion chelation.

These chelation events were monitored by using electrochemical methods and surface chemistry analysis and supported by theoretical calculations. We report a highly sensitive ion detection biosensor that can detect ions in the pM range.

This label-free and highly sensitive electrochemical detection technique holds a promise to be integrated with point of care facilities.