Electric stimulation induces morphogenetic elongation in a 3D embryo model*

Natural electrical cues in the form of ionic currents are increasingly understood to affect complex morphogenetic processes in multicellular organisms, spanning embryogenesis to skin healing. These cues can be externally harnessed to actually control such processes, as we have previously shown with control over collective cell migration and lumen formation in organoids. Here, we report on our new work applying biomimetic electrical cues (~1V/cm) to 3D aggregates of mouse embryonic stem cells, called ‘gastruloids’. While such structures will naturally recapitulate the mechanical elongation process associated with anterior-posterior (AP) axis formation during embryogenesis over several days, we found that electrical cues appear to dramatically accelerate this process, elongating strongly over a matter of hours in a process resembling AP formation.  In contrast to our prior work showing that hollow 3D epithelial ‘cysts’ swell isotropically under electric stimulation; gastruloids preferentially elongate parallel to the electric field axis, with the speed and extent of the deformation scaling with the strength of the applied field. Furthermore, we find that the growth dynamics are strongly influenced by the initial size, or age, of the gastruloid, suggesting that the mechanisms mediating this ‘electro-inflation’ vary during the course of gastruloid maturation. We present preliminary data characterizing key molecular and mechanical pathways of ‘electro-elongation’ using a combination of knock-out mutations and pharmacological inhibition and explore the role of electrostatic stresses by modeling the gastruloids using a modified Taylor-Melcher leaky dielectric model.