In this work, a surface-confined peptide network that can exhibit distinct structural features under protease cleavage and electrochemical treatment is developed as a highly sensitive biosensor for clinical detection of kallikrein 6 (KLK6). KLK6 is a serine protease of the tissue-remodeling process determining the development of hepatocellular carcinoma (HCC). The peptide network, immobilized on the electrode surface by a Au-S bond, loses its integrity upon KLK6 cleavage and is removed from the electrode by electrochemical desorption of thiol groups, while the network without protease cleavage can remain attached by a few intact Au-S bonds. In this manner, distinct conductivity of the electrode surface in the presence/absence of protease can result in a large signal-to-background ratio, enabling KLK6 detection in clinical samples. The detected KLK6 abundance can manifest the correlation between up-regulated KLK6 activity and the progress of HCC. These results suggest a potential future use of this peptide network as a biosensor to provide diagnostic information for better administration of HCC.
Keywords: electrochemical detection; extracellular matrix; hepatocellular carcinoma; kallikrein 6; peptide network.