Dept. Termodinàmica, Facultat de Física, Universitat de València, E-46100 Burjassot, Spain.
Dept. of Biology and Allen Discovery Center at Tufts University, Medford, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, USA.
Biochim Biophys Acta Gen Subj. 2023 Oct;1867(10):130440. doi: 10.1016/j.bbagen.2023.130440. Epub 2023 Jul 30.
Transmembrane electrical potential differences in cells modulate the spatio-temporal distribution of signaling ions and molecules that are instructive for downstream signaling pathways in multicellular systems. The local coupling between bioelectricity and protein transcription patterns allows dynamic subsystems (modules) of cells that share the same bioelectrical state to show similar biochemical downstream processes.
We simulate theoretically how the integration-segregation pattern formed by the different multicellular modules that define a biosystem can be controlled by multicellular potentials. To this end, we couple together the model equations of the bioelectrical network to those of the genetic network.
The coupling provided by the intercellular junctions and the external microenvironment allows the restoration of the target bioelectrical pattern by changing the transcription rate of specific ion channels, the post-translational blocking of these channels, and changes in the environmental ionic concentrations.
The simulations show that the single-cell feedback between bioelectrical and transcriptional processes, together with the coupling provided by the intercellular junctions and the environment, can correct large-scale patterns by means of suitable external actions.
This study provides a theoretical advancement in the understanding of how the multicellular bioelectric coupling may guide repolarizing interventions for regenerating a tissue, with potential implications in biomedicine.
细胞的跨膜电势能差异调节信号离子和分子的时空分布，这些离子和分子对多细胞系统中的下游信号通路具有指导意义。生物电与蛋白质转录模式之间的局部偶联允许具有相同生物电状态的细胞动态子系统（模块）表现出相似的生化下游过程。
我们从理论上模拟了由定义生物系统的不同多细胞模块形成的整合-分离模式如何可以通过多细胞电势来控制。为此，我们将生物电网络的模型方程与遗传网络的模型方程耦合在一起。
细胞间连接和外部微环境提供的耦合允许通过改变特定离子通道的转录率、这些通道的翻译后阻断以及环境离子浓度的变化来恢复目标生物电模式。
模拟表明，生物电和转录过程之间的单细胞反馈，以及细胞间连接和环境提供的耦合，可以通过适当的外部作用来纠正大规模模式。
这项研究提供了对多细胞生物电偶联如何指导组织再生的复极化干预的理解的理论进展，这在生物医学中有潜在的意义。
