Bioelectrical Coupling of Single-Cell States in Multicellular Systems

The spatiotemporal distributions of signaling ions and molecules that modulate biochemical pathways in nonexcitable cells are influenced by multicellular electric potentials. These potentials act as distributed controllers encoding instructive spatial patterns in development and regeneration. We review experimental facts and discuss recent bioelectrical models that provide new physical insights and complement biochemical approaches. Single-cell states are modulated at the multicellular level because of the coupling between neighboring cells, thus allowing memories and multicellular patterns. The model is based on (i) two generic voltage-gated ion channels that promote the polarized and depolarized cell states, (ii) a feedback mechanism for the transcriptional and bioelectrical regulations, and (iii) voltage-gated intercellular conductances that allow a dynamic intercellular connectivity. The simulations provide steady-state and oscillatory multicellular states that help explain aspects of development and guide experimental procedures attempting to establish instructive bioelectrical patterns based on electric potentials and currents to regulate cell behavior and morphogenesis.