Bioelectrical model of head-tail patterning based on cell ion channels and intercellular gap junctions. Author: Cervera J1, Meseguer S2, Levin M3, Mafe S4 Affiliation: <sup>1</sup>Dept. de Termodinàmica, Facultat de Física, Universitat de València, E-46100 Burjassot, Spain. Electronic address: jcervera@uv.es. <sup>2</sup>Laboratory of Immunobiology, Centro de Investigación Príncipe Felipe, Valencia 46012, Spain. <sup>3</sup>Allen Discovery Center at Tufts University, Department of Biology, Tufts University Medford, MA 02155-4243, United States. <sup>4</sup>Dept. de Termodinàmica, Facultat de Física, Universitat de València, E-46100 Burjassot, Spain. Conference/Journal: Bioelectrochemistry. Date published: 2019 Nov 29 Other: Volume ID: 132 , Pages: 107410 , Special Notes: doi: 10.1016/j.bioelechem.2019.107410. [Epub ahead of print] , Word Count: 222 Robust control of anterior-posterior axial patterning during regeneration is mediated by bioelectric signaling. However, a number of systems-level properties of bioelectrochemical circuits, including stochastic outcomes such as seen in permanently de-stabilized "cryptic" flatworms, are not completely understood. We present a bioelectrical model for head-tail patterning that combines single-cell characteristics such as membrane ion channels with multicellular community effects via voltage-gated gap junctions. It complements the biochemically-focused models by describing the effects of intercellular electrochemical coupling, cutting plane, and gap junction blocking of the multicellular ensemble. We provide qualitative insights into recent experiments concerning planarian anterior/posterior polarity by showing that: (i) bioelectrical signals can help separated cell domains to know their relative position after injury and contribute to the transitions between the abnormal double-head state and the normal head-tail state; (ii) the bioelectrical phase-space of the system shows a bi-stability region that can be interpreted as the cryptic system state; and (iii) context-dependent responses are obtained depending on the cutting plane position, the initial bioelectrical state of the multicellular system, and the intercellular connectivity. The model reveals how simple bioelectric circuits can exhibit complex tissue-level patterning and suggests strategies for regenerative control in vivo and in synthetic biology contexts. Copyright © 2019 Elsevier B.V. All rights reserved. KEYWORDS: Bioelectricity; Gap junctional communication; Head-tail patterning; Ion channel; Positional information; Regeneration PMID: 31821903 DOI: 10.1016/j.bioelechem.2019.107410