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细胞间生物电相互作用和遗传网络中的局部异质性:单细胞状态和多细胞振荡稳定的模型。

Cell-cell bioelectrical interactions and local heterogeneities in genetic networks: a model for the stabilization of single-cell states and multicellular oscillations.

机构信息

Dept. Termodinàmica, Fac. Física, Universitat de València, 46100 Burjassot, Spain.

出版信息

Phys Chem Chem Phys. 2018 Apr 4;20(14):9343-9354. doi: 10.1039/C8CP00648B.


DOI:10.1039/C8CP00648B
PMID:29564429
Abstract

Genetic networks operate in the presence of local heterogeneities in single-cell transcription and translation rates. Bioelectrical networks and spatio-temporal maps of cell electric potentials can influence multicellular ensembles. Could cell-cell bioelectrical interactions mediated by intercellular gap junctions contribute to the stabilization of multicellular states against local genetic heterogeneities? We theoretically analyze this question on the basis of two well-established experimental facts: (i) the membrane potential is a reliable read-out of the single-cell electrical state and (ii) when the cells are coupled together, their individual cell potentials can be influenced by ensemble-averaged electrical potentials. We propose a minimal biophysical model for the coupling between genetic and bioelectrical networks that associates the local changes occurring in the transcription and translation rates of an ion channel protein with abnormally low (depolarized) cell potentials. We then analyze the conditions under which the depolarization of a small region (patch) in a multicellular ensemble can be reverted by its bioelectrical coupling with the (normally polarized) neighboring cells. We show also that the coupling between genetic and bioelectric networks of non-excitable cells, modulated by average electric potentials at the multicellular ensemble level, can produce oscillatory phenomena. The simulations show the importance of single-cell potentials characteristic of polarized and depolarized states, the relative sizes of the abnormally polarized patch and the rest of the normally polarized ensemble, and intercellular coupling.

摘要

遗传网络在单细胞转录和翻译速率的局部异质性存在的情况下运作。生物电网络和细胞电潜力的时空图谱可以影响多细胞集合体。细胞间电连接介导的细胞间生物电相互作用是否有助于多细胞状态对抗局部遗传异质性的稳定?我们基于两个已确立的实验事实来从理论上分析这个问题:(i)膜电位是单细胞电状态的可靠读出,(ii)当细胞彼此连接时,它们的单个细胞电位可以受到集体平均电潜力的影响。我们提出了遗传和生物电网络之间耦合的最小生物物理模型,该模型将离子通道蛋白的转录和翻译速率中发生的局部变化与异常低(去极化)的细胞电位相关联。然后,我们分析了多细胞集合体中小区域(斑块)的去极化可以通过其与(正常极化)相邻细胞的生物电耦合来反转的条件。我们还表明,通过多细胞集合体水平的平均电潜力调制的非兴奋细胞的遗传和生物电网络之间的耦合可以产生振荡现象。模拟表明极化和去极化状态的单个细胞电位、异常极化斑块和其余正常极化集合体的相对大小以及细胞间耦合的重要性。

相似文献

[1]
Cell-cell bioelectrical interactions and local heterogeneities in genetic networks: a model for the stabilization of single-cell states and multicellular oscillations.

Phys Chem Chem Phys. 2018-4-4

[2]
Intercellular Connectivity and Multicellular Bioelectric Oscillations in Nonexcitable Cells: A Biophysical Model.

ACS Omega. 2018-10-31

[3]
From non-excitable single-cell to multicellular bioelectrical states supported by ion channels and gap junction proteins: Electrical potentials as distributed controllers.

Prog Biophys Mol Biol. 2019-6-27

[4]
Bioelectrical Signals and Ion Channels in the Modeling of Multicellular Patterns and Cancer Biophysics.

Sci Rep. 2016-2-4

[5]
Community effects allow bioelectrical reprogramming of cell membrane potentials in multicellular aggregates: Model simulations.

Phys Rev E. 2020-11

[6]
Oscillatory phenomena in electrophysiological networks: The coupling between cell bioelectricity and transcription.

Comput Biol Med. 2024-9

[7]
The interplay between genetic and bioelectrical signaling permits a spatial regionalisation of membrane potentials in model multicellular ensembles.

Sci Rep. 2016-10-12

[8]
Bioelectrical coupling in multicellular domains regulated by gap junctions: A conceptual approach.

Bioelectrochemistry. 2018-4-21

[9]
MicroRNA Intercellular Transfer and Bioelectrical Regulation of Model Multicellular Ensembles by the Gap Junction Connectivity.

J Phys Chem B. 2017-8-2

[10]
Bioelectrical Coupling of Single-Cell States in Multicellular Systems.

J Phys Chem Lett. 2020-5-7

引用本文的文献

[1]
Bioelectrical and cytoskeletal patterns correlate with altered axial polarity in the follicular epithelium of the Drosophila mutant gurken.

BMC Dev Biol. 2020-3-13

[2]
Endogenous Bioelectrics in Development, Cancer, and Regeneration: Drugs and Bioelectronic Devices as Electroceuticals for Regenerative Medicine.

iScience. 2019-12-20

[3]
Modeling somatic computation with non-neural bioelectric networks.

Sci Rep. 2019-12-9

[4]
Electrochemical gradients are involved in regulating cytoskeletal patterns during epithelial morphogenesis in the Drosophila ovary.

BMC Dev Biol. 2019-11-12

[5]
Electrochemical patterns during Drosophila oogenesis: ion-transport mechanisms generate stage-specific gradients of pH and membrane potential in the follicle-cell epithelium.

BMC Dev Biol. 2019-6-21

[6]
EDEn-Electroceutical Design Environment: Ion Channel Tissue Expression Database with Small Molecule Modulators.

iScience. 2019-1-25

[7]
Intercellular Connectivity and Multicellular Bioelectric Oscillations in Nonexcitable Cells: A Biophysical Model.

ACS Omega. 2018-10-31

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