Endogenous bioelectric patterns within tissues are an important driver of morphogenesis and a tractable component of a number of disease states. Developing system-level understanding of the dynamics by which non-neural bioelectric circuits regulate complex downstream cascades is a key step towards both, an evolutionary understanding of ion channel genes, and novel strategies in regenerative medicine. An important capability gap is deriving rational modulation strategies targeting individual cells’ bioelectric states to achieve global (tissue- or organ-level) outcomes. Here, we develop an ion channel-based model that describes multicellular states on the basis of spatio-temporal patterns of electrical potentials in aggregates of non-excitable cells. The model is of biological interest because modern techniques allow to associate bioelectrical signals with specific ion channel proteins in the cell membrane that are central to embryogenesis, regeneration, and tumorigenesis. As a complementary approach to the usual biochemical description, we have studied four biophysical questions: (i) how can single-cell bioelectrical states be established; (ii) how can a change in the cell potential caused by a transient perturbation of the cell state be maintained after the stimulus is gone (bioelectrical memory); (iii) how can a single-cell contribute to the control of multicellular ensembles based on the spatio-temporal pattern of electrical potentials; and (iv) how can oscillatory patterns arise from the single-cell bioelectrical dynamics. Experimentally, endogenous bioelectric gradients have emerged as instructive agents for morphogenetic processes. In this context, the simulations can guide new procedures that may allow a distributed control of the multicellular ensemble.

组织中的内源性生物电模式是形态发生的重要驱动力，并且是许多疾病状态的易处理成分。发展对非神经生物电路调节复杂下游级联反应动力学的系统级理解，是朝着离子通道基因的进化理解和再生医学新策略迈出的关键一步。一个重要的能力鸿沟是，推导针对单个细胞生物电态的合理调节策略，以实现整体（组织或器官水平）结果。在这里，我们开发了一个基于离子通道的模型，该模型基于非兴奋性细胞聚集体中电位的时空分布描述了多细胞状态。该模型具有生物学意义，因为现代技术允许将生物电信号与细胞膜中特定的离子通道蛋白相关联，这些蛋白是胚胎发生，再生和肿瘤发生的关键。作为对常规生化描述的补充方法，我们研究了四个生物物理问题：i）如何建立单细胞生物电状态；（ii）在刺激消失后，如何保持由细胞状态的短暂扰动引起的细胞电位变化（生物电记忆）；（iii）基于电位的时空分布，单细胞如何有助于控制多细胞集合体；（iv）如何从单细胞生物电动力学中产生振荡模式。实验上，内源性生物电梯度已成为形态发生过程的指导剂。在这种情况下，模拟可以指导新的程序，这些程序可能允许对多细胞集合体进行分布式控制。