Correcting instructive electric potential patterns in multicellular systems: External actions and endogenous processes

Abstract

Background: Transmembrane electrical potential differences in cells modulate the spatio-temporal distribution of signaling ions and molecules that are instructive for downstream signaling pathways in multicellular systems. The local coupling between bioelectricity and protein transcription patterns allows dynamic subsystems (modules) of cells that share the same bioelectrical state to show similar biochemical downstream processes. Methods: We simulate theoretically how the integration-segregation pattern formed by the different multicellular modules that define a biosystem can be controlled by multicellular potentials. To this end, we couple together the model equations of the bioelectrical network to those of the genetic network. Results: The coupling provided by the intercellular junctions and the external microenvironment allows the restoration of the target bioelectrical pattern by changing the transcription rate of specific ion channels, the post-translational blocking of these channels, and changes in the environmental ionic concentrations. Conclusions: The simulations show that the single-cell feedback between bioelectrical and transcriptional processes, together with the coupling provided by the intercellular junctions and the environment, can correct large-scale patterns by means of suitable external actions. General significance: This study provides a theoretical advancement in the understanding of how the multicellular bioelectric coupling may guide repolarizing interventions for regenerating a tissue, with potential implications in biomedicine.