Array-addressed scanning electrochemical cell microscopy for single-cell dual-cadherin profiling during epithelial-mesenchymal transition
- 1State Key Laboratory of Chemo/Biosensing and Chemometrics, Department of Chemistry and Chemical Engineering, Hunan University Changsha Hunan Province 410082 China
- 2State Key Lab of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University Nanjing 210093 China
Abstract
Single-cell electrochemical analysis provides a quantitative approach for resolving cellular heterogeneity, but conventional measurements on randomly distributed cells often suffer from inefficient target searching, limited positional control, and low statistical throughput. Herein, we report an aptamer-directed, dual-metal-tagged electrochemical strategy implemented on an array-addressed scanning electrochemical cell microscopy (SECCM) platform for targeted profiling of two surface proteins on individual cells. An ordered single-cell array was constructed on a poly(vinyl alcohol)-modified indium tin oxide (PVA-ITO) substrate using microcontact-printed polydopamine patterns, enabling deterministic positioning of the SECCM probe over predefined cells. E-cadherin (E-cad) and N-cadherin (N-cad), two representative surface markers of epithelial-mesenchymal transition (EMT), were selectively labeled with aptamer-functionalized silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs), respectively, producing well-separated stripping signals for dual-marker readout. Using transforming growth factor-β1-induced EMT in A549 cells as a model system, the platform quantitatively captured the expected cadherin switch at the single-cell level, with the E-cad-associated charge decreasing from 1.49 ± 0.38 to 0.23 ± 0.14 nC and the N-cad-associated charge increasing from 0.26 ± 0.16 to 1.01 ± 0.41 nC after EMT induction. Dual-marker scatter analysis further resolved epithelial-like, mesenchymal-like, and hybrid E+/N+ phenotypes, revealing EMT-associated cellular heterogeneity that is obscured in ensemble measurements. This work establishes an array-addressed SECCM strategy for aptamer-based dual-marker electrochemical detection of E-cad and N-cad on predefined individual cells, providing a general framework for single-cell surface-protein profiling.
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BibTeX
@article{zhang2026arrayaddressed,
title = {{Array-addressed scanning electrochemical cell microscopy for single-cell dual-cadherin profiling during epithelial-mesenchymal transition}},
author = {Yuanyuan Zhang and Meihong Peng and Pufeihong Xia and Yile Liu and Xing-Hua Xia and Yi-Ge Zhou},
journal = {Chemical science},
year = {2026},
month = oct,
doi = {10.1039/d6sc04444a},
url = {https://europepmc.org/article/PMC/PMC13720776},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Array-addressed scanning electrochemical cell microscopy for single-cell dual-cadherin profiling during epithelial-mesenchymal transition
AU - Yuanyuan Zhang
AU - Meihong Peng
AU - Pufeihong Xia
AU - Yile Liu
AU - Xing-Hua Xia
AU - Yi-Ge Zhou
PY - 2026
DA - 2026/10/23
JO - Chemical science
DO - 10.1039/d6sc04444a
UR - https://europepmc.org/article/PMC/PMC13720776
AB - Single-cell electrochemical analysis provides a quantitative approach for resolving cellular heterogeneity, but conventional measurements on randomly distributed cells often suffer from inefficient target searching, limited positional control, and low statistical throughput. Herein, we report an aptamer-directed, dual-metal-tagged electrochemical strategy implemented on an array-addressed scanning electrochemical cell microscopy (SECCM) platform for targeted profiling of two surface proteins on individual cells. An ordered single-cell array was constructed on a poly(vinyl alcohol)-modified indium tin oxide (PVA-ITO) substrate using microcontact-printed polydopamine patterns, enabling deterministic positioning of the SECCM probe over predefined cells. E-cadherin (E-cad) and N-cadherin (N-cad), two representative surface markers of epithelial-mesenchymal transition (EMT), were selectively labeled with aptamer-functionalized silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs), respectively, producing well-separated stripping signals for dual-marker readout. Using transforming growth factor-β1-induced EMT in A549 cells as a model system, the platform quantitatively captured the expected cadherin switch at the single-cell level, with the E-cad-associated charge decreasing from 1.49 ± 0.38 to 0.23 ± 0.14 nC and the N-cad-associated charge increasing from 0.26 ± 0.16 to 1.01 ± 0.41 nC after EMT induction. Dual-marker scatter analysis further resolved epithelial-like, mesenchymal-like, and hybrid E+/N+ phenotypes, revealing EMT-associated cellular heterogeneity that is obscured in ensemble measurements. This work establishes an array-addressed SECCM strategy for aptamer-based dual-marker electrochemical detection of E-cad and N-cad on predefined individual cells, providing a general framework for single-cell surface-protein profiling.
SN - 2041-6520
SN - 2041-6539
ER -