Dept. Termodinàmica, Fac. Física, Universitat de València, 46100 Burjassot, Spain.
Phys Chem Chem Phys. 2018 Apr 4;20(14):9343-9354. doi: 10.1039/C8CP00648B.
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.
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。
Bioelectrochemistry. 2018-4-21
J Phys Chem Lett. 2020-5-7
Sci Rep. 2019-12-9