Riol Alejandro, Cervera Javier, Levin Michael, Mafe Salvador
Dept. Termodinàmica, Facultat de Física, Universitat de València, E-46100 Burjassot, Spain.
Dept. of Biology, Allen Discovery Center at Tufts University, Medford, MA 02155-4243, USA.
Cancers (Basel). 2021 Oct 22;13(21):5300. doi: 10.3390/cancers13215300.
Electric potential distributions can act as instructive pre-patterns for development, regeneration, and tumorigenesis in cell systems. The biophysical states influence transcription, proliferation, cell shape, migration, and differentiation through biochemical and biomechanical downstream transduction processes. A major knowledge gap is the origin of spatial patterns in vivo, and their relationship to the ion channels and the electrical synapses known as gap junctions. Understanding this is critical for basic evolutionary developmental biology as well as for regenerative medicine. We computationally show that cells may express connexin proteins with different voltage-gated gap junction conductances as a way to maintain multicellular regions at distinct membrane potentials. We show that increasing the multicellular connectivity via enhanced junction function does not always contribute to the bioelectrical normalization of abnormally depolarized multicellular patches. From a purely electrical junction view, this result suggests that the reduction rather than the increase of specific connexin levels can also be a suitable bioelectrical approach in some cases and time stages. We offer a minimum model that incorporates effective conductances ultimately related to specific ion channel and junction proteins that are amenable to external regulation. We suggest that the bioelectrical patterns and their encoded instructive information can be externally modulated by acting on the mean fields of cell systems, a complementary approach to that of acting on the molecular characteristics of individual cells. We believe that despite the limitations of a biophysically focused model, our approach can offer useful qualitative insights into the collective dynamics of cell system bioelectricity.
电势分布可作为细胞系统中发育、再生和肿瘤发生的指导性预模式。生物物理状态通过生化和生物力学下游转导过程影响转录、增殖、细胞形态、迁移和分化。一个主要的知识空白是体内空间模式的起源,以及它们与离子通道和被称为缝隙连接的电突触的关系。理解这一点对于基础进化发育生物学以及再生医学至关重要。我们通过计算表明,细胞可能表达具有不同电压门控缝隙连接电导的连接蛋白,以此来维持多细胞区域处于不同的膜电位。我们表明,通过增强连接功能来增加多细胞连接性并不总是有助于异常去极化的多细胞斑块的生物电正常化。从纯粹的电连接角度来看,这一结果表明,在某些情况和时间阶段,降低而非增加特定连接蛋白水平也可能是一种合适的生物电方法。我们提供了一个最小模型,该模型纳入了最终与特定离子通道和连接蛋白相关的有效电导,这些电导易于受到外部调节。我们建议,可以通过作用于细胞系统的平均场来外部调节生物电模式及其编码的指导性信息,这是一种与作用于单个细胞分子特征互补的方法。我们相信,尽管以生物物理为重点的模型存在局限性,但我们的方法可以为细胞系统生物电的集体动力学提供有用的定性见解。
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