For over a decade, Zhao has been studying how cells migrate in response to electrical fields. It has been a lonely field, however. Electricity does not fit easily into the gene–protein paradigm of cellular control, and the field's reputation was tainted by some poorly controlled experiments conducted early in the 20th century.
Now, Zhao and colleagues have confirmed claims first made more than 150 years ago that wounds generate electrical fields. There is normally a potential difference between basal tissue layers and apical skin surface—a difference generated by transport of Cl− ions outwards and Na+ ions inwards. But this potential difference is short circuited by a wound. The wounded basal edge becomes electrically more like an apical surface, so that now the potential difference is between this damaged basal edge and the undamaged, internal basal tissue. The result is an electrical field directed into the wound.
The researchers found that electrical fields of this magnitude could direct cell migration both in vitro and in vivo, either slowing or accelerating wound healing, depending on the field directionality. The correlation between the magnitudes of naturally occurring and experimentally effective field potentials “got us more and more excited and thinking this is a real phenomenon,” says Zhao.
The pathway required PI3Kγ and was enhanced by loss of PTEN. These proteins are well known as mediators of chemotactic signaling, but with a whole genome screen the group hopes to discover molecules unique to electrotaxis.