Colorimetric Detection of Met Dimerization on Live Cells via Smartphone for High-Sensitivity Sensing of the HGF/Met Signaling Pathway.

Membrane protein dimerization regulates numerous cellular biological processes; therefore, highly sensitive and facile detection of membrane protein dimerization are very crucial for clinical diagnosis and biomedical research. Herein, a colorimetric detection of Met dimerization on live cells via smartphone for high-sensitivity sensing of the HGF/Met signaling pathway was developed for the first time. The Met monomers on live cells were recognized by specific ligands (aptamers) first, and the Met dimerizations triggered the proximity-ligation-assisted catalytic hairpin assembly (CHA) reaction to generate large amounts of G-quadruplex (G4) fragments which can further combine hemin to form G4/hemin DNAzymes possessing the horseradish-peroxidase-like catalytic activity for catalyzing the oxidation of ABTS by H 2 O 2 and producing the colorimetric signal (i.e., color change). The colorimetric detection of Met on live cells was then achieved by image acquisition and processing via a smartphone. As a proof-of-principle, the HGF/Met signaling pathway based on Met-Met dimerization was facile monitored, and the human gastric cancer cells MKN-45 with natural Met-Met dimers were sensitively tested and a wide linear working range from 2 to 1000 cells with a low detection limit of 1 cell was obtained. The colorimetric assay possesses a good specificity and high recovery rate of MKN-45 cells spiked in peripheral blood, which indicates that the proposed colorimetric detection of Met dimerization can be used for convenient observation of the HGF/Met signaling pathway and has extensive application prospects in point-of-care testing (POCT) of Met-dimerization-related tumor cells.