Intercellular Connectivity and Multicellular Bioelectric Oscillations in Nonexcitable Cells: A Biophysical Model

Bioelectricity is emerging as a crucial mechanism for signal transmission and processing from the single-cell level to multicellular domains. We explore theoretically the oscillatory dynamics that result from the coupling between the genetic and bioelectric descriptions of nonexcitable cells in multicellular ensembles, connecting the genetic prepatterns defined over the ensemble with the resulting spatio-temporal map of cell potentials. These prepatterns assume the existence of a small patch in the ensemble with locally low values of the genetic rate constants that produce a specific ion channel protein whose conductance promotes the cell-polarized state (inward-rectifying channel). In this way, the short-range interactions of the cells within the patch favor the depolarized membrane potential state, whereas the long-range interaction of the patch with the rest of the ensemble promotes the polarized state. The coupling between the local and long-range bioelectric signals allows a binary control of the patch membrane potentials, and alternating cell polarization and depolarization states can be maintained for optimal windows of the number of cells and the intercellular connectivity in the patch. The oscillatory phenomena emerge when the feedback between the single-cell bioelectric and genetic dynamics is coupled at the multicellular level. In this way, the intercellular connectivity acts as a regulatory mechanism for the bioelectrical oscillations. The simulation results are qualitatively discussed in the context of recent experimental studies.