Target-Triggered Molecular Domino Effect: A Programmable Peptide Self-Assembly Induced Signal Amplification System.

Abstract

In nature, biological systems achieve highly efficient sensing through the orchestrated self-assembly of proteins, which converts subtle molecular stimuli into clear physiological responses. However, replicating such high-fidelity transduction in artificial peptide-based sensors remains a challenge. Herein, we report a programmable "Molecular Domino" strategy that transforms peptide assembly from a passive recognition event into an active, cascaded signal amplification process. Specifically, we have designed a self-assembling peptide (SAP-RGD) that remains kinetically monodispersed until the target acts as a local nucleation template, overcoming the energy barrier to initiate in situ assembly. This initial recognition event triggers a domino-like effect: target-anchored assemblies act as molecular seeds for the recursive recruitment of peptide monomers (RRK-SAP), which subsequently bridge silver nanoparticles (AgNPs) to generate a high-gained electrochemical signal. This bioinspired approach has also demonstrated exceptional sensitivity for breast cancer cell detection and robust performance in complex biological matrices. Furthermore, by modularly tailoring the targeting motif, the designed system has successfully monitored the dynamic expression of N-cadherin during the epithelial-to-mesenchymal transition (EMT) in MCF-7 cells. This modular sensing paradigm may offer a versatile method for precisely tracking complex pathological transitions.