Dept. de Termodinàmica, Facultat de Física, Universitat de València, E-46100 Burjassot, Spain.
Laboratory of Immunobiology, Centro de Investigación Príncipe Felipe, Valencia 46012, Spain.
Bioelectrochemistry. 2020 Apr;132:107410. doi: 10.1016/j.bioelechem.2019.107410. Epub 2019 Nov 29.
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.
生物电信号在再生过程中对前后轴模式的稳健控制。然而,生物电化学电路的许多系统级特性,包括永久性不稳定的“隐匿”扁形虫中出现的随机结果,还不完全清楚。我们提出了一个用于头尾模式的生物电模型,该模型将细胞膜离子通道等单细胞特性与电压门控间隙连接的多细胞群落效应相结合。它通过描述细胞间电化学耦合、切割面和多细胞集合的间隙连接阻断的影响,补充了以生物化学为重点的模型。我们通过展示以下内容,为最近有关扁形虫前后极性的实验提供了定性的见解:(i)生物电信号可以帮助分离的细胞区域在受伤后了解它们的相对位置,并有助于异常双头状态和正常头尾状态之间的转变;(ii)系统的生物电相空间显示出双稳定性区域,可以解释为隐匿系统状态;(iii)根据切割面位置、多细胞系统的初始生物电状态和细胞间连接性,获得了上下文相关的响应。该模型揭示了简单的生物电路如何表现出复杂的组织级模式,并为体内和合成生物学背景下的再生控制提供了策略。
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