Harnessing Electric Fields: A New Frontier in Guiding Embryonic Cell Movement

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As an embryo matures, a constant exchange of information occurs between cells to construct tissues and organs. Cells must detect numerous signals from their surroundings, which may be chemical or mechanical in origin. However, these alone cannot fully elucidate collective cell movement, and substantial evidence indicated that motion may also be influenced by embryonic electric fields. How and where these fields are established within embryos remained uncertain until recently. “We have characterized an endogenous bioelectric current pattern that resembles an electric field during development, demonstrating that this current can guide the migration of a cell cluster known as the neural crest,” states Dr. Elias H. Barriga, the lead author behind the study. Initially, Dr. Barriga and his team started their research on the neural crest at the former Gulbenkian Institute of Science (IGC) in Oeiras, Portugal before continuing their work in Dresden, forming a team at the Cluster of Excellence Physics of Life.

The neural crest is an integral component of the embryo, with this grouping of cells responsible for forming the bones of the face and neck, alongside certain parts of the nervous system. Dr. Barriga and associates discovered that neural crest cells are guided by internal electric fields throughout development, akin to drivers following a traffic officer’s signs. The team found that through this mechanism, known as electrotaxis, cells can detect direction from electric fields generated internally within the embryo and move accordingly. Previously, this phenomenon had primarily been limited to studies involving cultured cells, but it has now been demonstrated within a developing embryo. Nonetheless, a crucial question remained unanswered: How do the cells interpret these currents and convert them into directional movement?

To provide answers, Dr. Barriga and his team located an enzyme known as voltage-sensitive phosphatase 1 (Vsp1) present in neural crest cells. Due to the adaptable structure of Vsp1, it appeared to have the capability of both detecting and transducing electrical signals. To validate that Vsp1 is necessary for electrotaxis, the researchers engineered a faulty variant of the enzyme and demonstrated that collective electrotaxis was hindered in cells injected with this version. “Utilizing tools I developed to target gene expression in the context of bioelectricity was tremendously fulfilling, and I eagerly anticipate its full potential being realized,” emphasized Dr. Sofia Moreira, a postdoctoral researcher involved in the study. Contrary to initial expectations, Vsp1 did not seem relevant to the movement itself, but rather could specifically convert electric current gradients into directives for directional and group migration. This is a distinctive finding, as most enzyme sensors are essential for movement, complicating the analysis of their role in steering direction. Taking it a step further, the authors also proposed how electric fields may be generated; through mechanical stretching of a zone referred to as the neural fold. As the cells within this area elongate, specific ion channels become activated, leading to a voltage gradient. When cells encounter this gradient, Vsp1 converts the electrical signals into directional guidance, instructing the cells on where to go, resulting in collective cell migration.

This represents the first experimental evidence indicating that electric fields arise along the route that neural crest cells migrate, and elucidates their mechanism of origin. These findings emphasize the significant contribution that bioelectricity makes during embryonic development. By enhancing our understanding of electrotaxis within a living organism, this research opens up new avenues for replicating developmental processes in laboratory settings with unprecedented accuracy. The first author of the study, postdoctoral researcher Dr. Fernando Ferreira remarks, “This paper bridges an important and long-standing gap in bioelectricity research, and it is immensely gratifying to be a part of the ongoing revival in developmental bioelectricity.” Nevertheless, studies into the mechanisms of electrotaxis remain in progress. “From a broader standpoint, we have now added another factor into the complex process of tissue morphogenesis,” observes Dr. Barriga. “The current question is how does this integrate with already established frameworks of mechanical and chemical signals during embryonic formation?” Beyond development, similar mechanisms may also manifest during wound healing and cancer progression. Grasping how electric fields influence cell migration could even inspire innovative strategies in tissue engineering and regenerative medicine. However, further exploration is essential to expand on the role of electric fields in cellular behavior and enhance our understanding of the physics underlying living systems.

Reference: Ferreira F, Moreira S, Zhao M, Barriga EH. Stretch-induced endogenous electric fields drive directed collective cell migration in vivo. Nat Mater. 2025. doi: 10.1038/s41563-024-02060-2

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