Bioelectrical regionalization of multicellular aggregates by microRNAs

We theoretically explore how microRNAs (miRNAs) can modulate the expression of ion channel proteins and the resulting cell membrane potentials in multicellular aggregates. To this end, we simulate the spatiotemporal regionalizations that characterize experimentally instructive bioelectrical states. Instead of focusing on a particular biological system, we consider a simple but illustrative biophysical model for the interplay between genetics and bioelectricity at the single-cell level. At the multicellular level, the assumed intercellular connectivity can establish spatiotemporal patterns of coupled bioelectrical and transcriptional states. The resulting distributed control exerts a significant influence on protein expression in multicellular aggregates, establishing instructive maps for development and regeneration. The system dynamics are simulated in spatially inhomogeneous aggregates under different miRNA production rates and intercellular connectivity. The results allow a qualitative understanding of the context-dependent effects observed when signaling biomolecules are spatially regionalized and transferred through intercellular junctions under the influence of multicellular electrical potentials.