Bioelectrical patterns are established by spatiotemporal correlations of cell membrane potentials at the multicellular level, being crucial to development, regeneration, and tumorigenesis. We have conducted multicellular simulations on bioelectrical community effects and intercellular coupling in multicellular aggregates. The simulations aim at establishing under which conditions a local heterogeneity consisting of a small patch of cells can be stabilized against a large aggregate of surrounding identical cells which are in a different bioelectrical state. In this way, instructive bioelectrical information can be persistently encoded in spatiotemporal patterns of separated domains with different cell polarization states. The multicellular community effects obtained are regulated both at the single-cell and intercellular levels, and emerge from a delicate balance between the degrees of intercellular coupling in: (i) the small patch, (ii) the surrounding bulk, and (iii) the interface that separates these two regions. The model is experimentally motivated and consists of two generic voltage-gated ion channels that attempt to establish the depolarized and polarized cell states together with coupling conductances whose individual and intercellular different states permit a dynamic multicellular connectivity. The simulations suggest that community effects may allow the reprogramming of single-cell bioelectrical states, in agreement with recent experimental data. A better understanding of the resulting electrical regionalization can assist the electroceutical correction of abnormally depolarized regions initiated in the bulk of normal tissues as well as suggest new biophysical mechanisms for the establishment of target patterns in multicellular engineering.

中文翻译：

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群落效应允许多细胞聚集体中细胞膜电位的生物电重编程：模型模拟

生物电模式是通过多细胞水平上细胞膜电位的时空相关性建立的，对发育、再生和肿瘤发生至关重要。我们已经对多细胞聚集体中的生物电群落效应和细胞间耦合进行了多细胞模拟。模拟旨在确定在何种条件下，由一小块细胞组成的局部异质性可以稳定，对抗周围处于不同生物电状态的大量相同细胞。通过这种方式，可以在具有不同细胞极化状态的分离域的时空模式中持续编码具有指导意义的生物电信息。获得的多细胞群落效应在单细胞和细胞间水平上均受到调节，并从以下细胞间耦合程度之间的微妙平衡中出现：（i）小块，（ii）周围的体积，以及（iii）分隔这两个区域的界面。该模型由实验驱动，由两个通用电压门控离子通道组成，这些通道试图建立去极化和极化细胞状态以及耦合电导，其个体和细胞间不同状态允许动态多细胞连接。模拟表明，群落效应可能允许对单细胞生物电状态进行重新编程，这与最近的实验数据一致。