2. Academic Validation
  3. Osmotic Tension Asymmetry Drives Electrotactic Migration via PDLIM7-Polarized Microfilament Coordination in Breast Cancer Cells

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

  • Adv Sci (Weinh). 2025 Dec 22:e15246. doi: 10.1002/advs.202515246.
Ling Zhu 1 2,  Zihui Zheng 1 2,  Wang Li 1 2,  Chenyi Shou 1 2,  Ying Zhao 1 2,  Lijun Zhang 1 2,  Xiaoli Shi 1 2,  Yunfeng Hu 1 2,  Huanhuan Zhao 3,  Huiwen Wu 4,  Jun Guo 1 2
Affiliations

Affiliations

  • 1 State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, P. R. China.
  • 2 Department of Biochemistry and Molecular Biology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, P. R. China.
  • 3 Basic Medical Experiment Center, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, P. R. China.
  • 4 Laboratory Center for Basic Medical Sciences, Nanjing Medical University, Nanjing, P. R. China.
PMID: 41431193 DOI: 10.1002/advs.202515246
Abstract

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.

Keywords

PDLIM7; breast cancer; directional migration; electrotaxis; osmotic pressure asymmetry.

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