Molecular tension tether based on electrochemiluminescence sensor for cellular mechanics measurement

Cellular mechanical force, produced by actomyosin contractility and actin polymerization, are transmitted to extracellular matrix ligands and neighboring cells. It is essential for processes such as cell adhesion, migration, morphogenesis and differentiation. Here, we developed a molecular tension gauge tether (TGT) platform for measuring cellular mechanical force based on ultrasensitive electrochemical luminescence (ECL) sensor. It engaged TGT with cellular mechanical force-driven toehold-mediated strand displacement (F-TSDR) and catalytic hairpin assembly (CHA) amplification. When the integrin of the fibroblast membrane is successfully recognized by the integrin ligand (cRGDfk) in TGT, the duplex split irreversibly by cellular mechanical force. The F-TSDR and CHA amplification can be converted into ECL signals. Additionally, Pt@La-MOF with high ECL efficiency was used as the anode luminescent unit. During the F-TSDR process, if the cellular mechanical force exceeds the tension threshold (T_tol), the cell receptor effectively triggers mechanical denaturation of the S1-S2-RT1 probe (unzipping mode, T_tol ∼12 pN) to release S2, the CHA cycle begins, leading to the quenching of the ECL signal from the luminescent unit ("on" to "off"). If the cellular mechanical force is below T_tol (shearing mode, T_tol ∼56 pN). It does not trigger the structural denaturation of the S1-S2-RT2 probe to release S2, resulting in no ECL signal change. This work develops a model that converts cellular mechanical force into ECL signals, ranging from 12 to 56 pN. It provides a novel and highly sensitive ECL sensor for cellular mechanical force measurement on cellular metastasis research and anti-adhesion drug screening.