Yildiz, Solen KumbayAkar, SametOzturk, EmreDincer, PervinUyanik, IsmailDuz, Nilufer2026-03-062026-03-0620262054-5703https://hdl.handle.net/20.500.12416/15890https://doi.org/10.1098/rsos.251001Mechanical stretch is a fundamental regulator of cell fate, yet in vitro replication remains challenging because conventional stretchers deliver non-uniform strain and ignore batch-to-batch variations in substrate stiffness-so the stress actually experienced by cells varies unpredictably. We introduce the first biaxial cell-stretching platform that couples an embedded soft resistive micro-channel sensor with high-frequency closed-loop control. Real-time deformation read-out (60 Hz) drives a 24 kHz actuator loop to compensate for polydimethylsiloxane (PDMS) moduli spanning an order of magnitude, delivering user-defined triangular or square waveforms (5-20% amplitude; 0.5-10 s period) with less than 2% steady-state error. Closed-loop operation maintains strain-invariant membrane stress within +/- 5%, reducing well-to-well variability threefold compared with open-loop actuation. Biological validation using immortalized human myoblasts exposed to 10% cyclic stretch for 4 h produced a significant upregulation of YAP/TAZ target genes (C-MYC, MYL9, DIAPH1, ANKRD1; p < 0.001), confirming mechanotransductive efficacy. The platform's modular architecture accommodates stiffness-tunable hydrogels and live imaging, offering a reproducible tool for mechanobiology, tissue engineering, disease modelling and personalized mechanotherapy.eninfo:eu-repo/semantics/openAccessMechanobiologyBiaxial Cell StretchingSkeletal Muscle CellsSoft Strain SensorClosed-Loop ControlMechanotransductionArticle10.1098/rsos.251001