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Cell Systems Bioelectricity: How Different Intercellular Gap Junctions Could Regionalize a Multicellular Aggregate
SIMPLE SUMMARY: Electric potential patterns across tissues are instructive for development, regeneration, and tumorigenesis because they can influence transcription, migration, and differentiation through biochemical and biomechanical downstream processes. Determining the origins of the spatial doma...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582473/ https://www.ncbi.nlm.nih.gov/pubmed/34771463 http://dx.doi.org/10.3390/cancers13215300 |
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author | Riol, Alejandro Cervera, Javier Levin, Michael Mafe, Salvador |
author_facet | Riol, Alejandro Cervera, Javier Levin, Michael Mafe, Salvador |
author_sort | Riol, Alejandro |
collection | PubMed |
description | SIMPLE SUMMARY: Electric potential patterns across tissues are instructive for development, regeneration, and tumorigenesis because they can influence transcription, migration, and differentiation through biochemical and biomechanical downstream processes. Determining the origins of the spatial domains of distinct potential, which in turn decide anatomical features such as limbs, eyes, brain, and heart, is critical to a mature understanding of how bioelectric signaling drives morphogenesis. We studied theoretically how connexin proteins with different voltage-gated gap junction conductances can maintain multicellular regions at distinct membrane potentials. We analyzed a minimal model that incorporates effective conductances ultimately related to specific ion channel and junction proteins that are amenable to external regulation. We also consider a bioelectrical relationship between the connexin composition of the intercellular gap junction and different stages of cancer. ABSTRACT: Electric potential distributions can act as instructive pre-patterns for development, regeneration, and tumorigenesis in cell systems. The biophysical states influence transcription, proliferation, cell shape, migration, and differentiation through biochemical and biomechanical downstream transduction processes. A major knowledge gap is the origin of spatial patterns in vivo, and their relationship to the ion channels and the electrical synapses known as gap junctions. Understanding this is critical for basic evolutionary developmental biology as well as for regenerative medicine. We computationally show that cells may express connexin proteins with different voltage-gated gap junction conductances as a way to maintain multicellular regions at distinct membrane potentials. We show that increasing the multicellular connectivity via enhanced junction function does not always contribute to the bioelectrical normalization of abnormally depolarized multicellular patches. From a purely electrical junction view, this result suggests that the reduction rather than the increase of specific connexin levels can also be a suitable bioelectrical approach in some cases and time stages. We offer a minimum model that incorporates effective conductances ultimately related to specific ion channel and junction proteins that are amenable to external regulation. We suggest that the bioelectrical patterns and their encoded instructive information can be externally modulated by acting on the mean fields of cell systems, a complementary approach to that of acting on the molecular characteristics of individual cells. We believe that despite the limitations of a biophysically focused model, our approach can offer useful qualitative insights into the collective dynamics of cell system bioelectricity. |
format | Online Article Text |
id | pubmed-8582473 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85824732021-11-12 Cell Systems Bioelectricity: How Different Intercellular Gap Junctions Could Regionalize a Multicellular Aggregate Riol, Alejandro Cervera, Javier Levin, Michael Mafe, Salvador Cancers (Basel) Article SIMPLE SUMMARY: Electric potential patterns across tissues are instructive for development, regeneration, and tumorigenesis because they can influence transcription, migration, and differentiation through biochemical and biomechanical downstream processes. Determining the origins of the spatial domains of distinct potential, which in turn decide anatomical features such as limbs, eyes, brain, and heart, is critical to a mature understanding of how bioelectric signaling drives morphogenesis. We studied theoretically how connexin proteins with different voltage-gated gap junction conductances can maintain multicellular regions at distinct membrane potentials. We analyzed a minimal model that incorporates effective conductances ultimately related to specific ion channel and junction proteins that are amenable to external regulation. We also consider a bioelectrical relationship between the connexin composition of the intercellular gap junction and different stages of cancer. ABSTRACT: Electric potential distributions can act as instructive pre-patterns for development, regeneration, and tumorigenesis in cell systems. The biophysical states influence transcription, proliferation, cell shape, migration, and differentiation through biochemical and biomechanical downstream transduction processes. A major knowledge gap is the origin of spatial patterns in vivo, and their relationship to the ion channels and the electrical synapses known as gap junctions. Understanding this is critical for basic evolutionary developmental biology as well as for regenerative medicine. We computationally show that cells may express connexin proteins with different voltage-gated gap junction conductances as a way to maintain multicellular regions at distinct membrane potentials. We show that increasing the multicellular connectivity via enhanced junction function does not always contribute to the bioelectrical normalization of abnormally depolarized multicellular patches. From a purely electrical junction view, this result suggests that the reduction rather than the increase of specific connexin levels can also be a suitable bioelectrical approach in some cases and time stages. We offer a minimum model that incorporates effective conductances ultimately related to specific ion channel and junction proteins that are amenable to external regulation. We suggest that the bioelectrical patterns and their encoded instructive information can be externally modulated by acting on the mean fields of cell systems, a complementary approach to that of acting on the molecular characteristics of individual cells. We believe that despite the limitations of a biophysically focused model, our approach can offer useful qualitative insights into the collective dynamics of cell system bioelectricity. MDPI 2021-10-22 /pmc/articles/PMC8582473/ /pubmed/34771463 http://dx.doi.org/10.3390/cancers13215300 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Riol, Alejandro Cervera, Javier Levin, Michael Mafe, Salvador Cell Systems Bioelectricity: How Different Intercellular Gap Junctions Could Regionalize a Multicellular Aggregate |
title | Cell Systems Bioelectricity: How Different Intercellular Gap Junctions Could Regionalize a Multicellular Aggregate |
title_full | Cell Systems Bioelectricity: How Different Intercellular Gap Junctions Could Regionalize a Multicellular Aggregate |
title_fullStr | Cell Systems Bioelectricity: How Different Intercellular Gap Junctions Could Regionalize a Multicellular Aggregate |
title_full_unstemmed | Cell Systems Bioelectricity: How Different Intercellular Gap Junctions Could Regionalize a Multicellular Aggregate |
title_short | Cell Systems Bioelectricity: How Different Intercellular Gap Junctions Could Regionalize a Multicellular Aggregate |
title_sort | cell systems bioelectricity: how different intercellular gap junctions could regionalize a multicellular aggregate |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582473/ https://www.ncbi.nlm.nih.gov/pubmed/34771463 http://dx.doi.org/10.3390/cancers13215300 |
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