Field-mediated Bioelectric Basis of Morphogenetic Prepatterning: a computational study

Bioelectric communication among cells plays an important role in numerous morphogenetic processes. Computational modeling and experimental modulation of these processes have largely focused on a discrete, localized view of cells and intercellular networks determining spatio-temporal patterns of resting membrane potential (Vmem) within tissues. Here we characterize novel contributions of the electrostatic force field, a continuous and pervasive entity existing within living tissues and modulating intercellular interactions. We consider a minimal but biologically-plausible non-neural bioelectric network model endowed with an electrostatic field where the Vmem of a cell is regulated by the average strength of the surrounding field via negative feedback. A detailed examination of this model revealed that the field systematically regulates key statistical and dynamical characteristics of spatiotemporal configurations of Vmem patterns such as complexity, dimensionality and causality by leveraging a mechanism akin to “synergetics” where it simultaneously forms a lower-dimensional projection of the pattern and enhances the causal strength and distance among its components. Moreover, the almost instantly-penetrating nature of the field endows the system with a unique amenability to self-organize complex positional information patterns following a transient stimulation of just the boundary of the tissue – an organizer-like property that suggests new avenues for modulation in biomedical contexts. We used automatic differentiation-based machine learning methods to optimize signals from a symmetry-breaking organizer region which would induce development of a vertebrate face prepattern. A detailed spatiotemporal dynamical analysis of a pair of such models with differing degrees of field-sensitivity revealed very different collective coordination strategies with which the model developed the pattern, namely, a ‘preformed’ mosaic mechanism and an ‘emergent’ stigmergic mechanism. The stigmergic pattern, in particular, recapitulated several key features of the developmental sequence of the bioelectric facial prepattern observed in frog embryos. These results highlight the promising potential of the electric field per se as a facilitator of collective patterning, providing a kind of master regulator interventional target for applications in regenerative medicine and bioengineering.