Osmotic Tension Asymmetry Drives Electrotactic Migration via PDLIM7-Polarized Microfilament Coordination in Breast Cancer Cells

Directional migration of tumor cells depends on mechanical forces generated by intracellular asymmetry. This study establishes an electric field-induced directional migration model using fluorescence tension probes to visualize microfilament forces and intracellular osmotic pressure dynamics. Electric fields induce protein kinase A (PKA)-dependent PDLIM7 recruitment, polarizing microfilament tension at cell edges via site-specific phosphorylation at serine 190. Concurrently, the electric field induces asymmetric changes in membrane potential, driven by protein nanoparticles and calcium ions, regulating osmotic tension. Leading-edge depolarization activates TMEM16A channel, while trailing-edge hyperpolarization activates the small conductance calcium-activated potassium (SK) channel. Chloride influx and potassium efflux create differential ion diffusion, resulting in leading-edge hypertonic expansion and trailing-edge contraction, thereby dictating the directionality of electrotactic migration. Osmotic pressure asymmetry further modulates PKA polarity, amplifying directional migration cues. This study elucidates the coordinated interplay between osmotic tension and membrane potential in cellular electromechanics, revealing a mechanistic framework where osmotic tension asymmetry orchestrates tumor cell migration through polarized PDLIM7-microfilament tension regulation.