Electric field modulation of integrin polarization and directed cell migration

Electrical stimulation is clinically used for the treatment of pain and to promote wound healing. In orthopaedic practices, applied electric fields (EFs) promote bone healing and improve lapine ligament repair in vivo. In the current study, several stimulation waveforms used in physical therapy were adapted to examine their effects on anterior cruciate ligament fibroblast (ACLF) migration and morphology. Most of the waveforms we tested resulted in enhanced fibroblast migration, while their effects on migration directionality were noticeably different. Furthermore, ACLFs elongation and alignment were only found in the DC groups. These findings suggest a decoupling of migration speed and directionality, which may arise from disparate mechanisms. We found that integrin acts as a major player of EF-induced directionality. We also found that integrin redistribution mediate the cathodal redistribution of RhoA. This introduces EF mediates one of the major signaling molecules, which is downstream from the integrin asymmetrically, with stronger redistribution on the cathode, is highly significant functionally. Results from this study may benefit our understanding the electro-therapy treatment on cell behavior and the relation between integrin and EF-induced directionality.