The Interplay of Electric Potential and Morphology of Biomembranes - Supplement

摘要 质膜上的电势差对所有活细胞来说都是常见的，对于 产生细胞间通讯的动作电位。在兴奋的神经和肌肉细胞之外， 与跨膜电位共轭的生物电信号控制许多细胞行为，如迁移， 定向和增殖在胚胎发生中起着关键作用，它们会促进愈合和癌症的进展。 细胞对电刺激的反应机制在很大程度上是未知的。以电为中心的观点， 以Hodgkin-Huxley模型为代表，主要研究电压相关的离子通道。然而，在最近 多年来，膜力学正在成为一个潜在的重要参与者：膜变形 被检测为与动作电位共同传播的几个离子通道被发现既是电压通道，也是电压通道。 门控和机械敏感，以及脂筏被认为是电子传感器。对该计划的评估 这些与膜相关的效应与生物电现象的相关性需要基本理解 膜的形态、应力和电压之间的耦合是有限的。 为了填补这一空白，我们采取了理论和实验相结合的方法来研究仿生 在外加电场作用下产生跨膜电位的膜。具体地说， 研究试图确定膜电位和电荷是如何引起膜反应的 拉伸或压缩、曲率和相变，反之亦然，膜如何变化 形态对跨膜电位有调节作用。从数学上讲，这些都是对自由边界的挑战 表现出复杂动力学的问题。连续介质理论将被用来模拟离子的输运，运动 荷电脂质膜界面及周围液体。正在开发一种计算方法来 解决这些复杂的瞬变三维自由边界问题。研究了极限情况 在分析上，使用渐近和摄动方法。实验中，使用巨大的单层囊泡 (Guv)作为膜系统的模型，我们开发了新的方法来探索动态耦合。 生物膜的形状和电压之间的关系。这些技术是基于闪烁光谱学的 (热驱动微米和亚微米薄膜波动的分析)和GUV变形 外加电场。我们将研究具有广泛组成范围的模拟生物膜 膜。实验结果将为数学模型提供相关的物理和 材料参数，反之亦然，理论将为实验提供指导。 利用光学显微镜对GUV动力学进行了可视化。因此，这项补充建议 请求提供资金，以支持购买专门用于这些研究的新显微镜。

SUMMARY An electric potential difference across the plasma membrane is common to all living cells and is crucial for the generation of action potentials for cell-to-cell communication. Beyond excitable nerve and muscle cell, bioelectric signals conjugated with the transmembrane potential control many cell behaviors such as migration, orientation, and proliferation, which play crucial role in embryogenesis, would healing, and cancer progression. The mechanisms of cellular responses to electric stimuli are largely unknown. An electricity-centered view, epitomized by the Hodgkin-Huxley model, focuses on the voltage-dependent ion channels. However, in recent years membrane mechanics is emerging as a potentially important player: membrane deformations are detected to co-propagate with action potentials, several ion channels have been found to be both voltage- gated and mechanosensitive, and lipid rafts have been implicated as electrosensors. Assessment of the relevance of these membrane-related effects in bioelectric phenomena requires fundamental understanding of the coupling between membrane morphology, stresses, and voltage, which is limited. To fill this void, we take a combined theoretical and experimental approach to study of biomimetic membranes with transmembrane potential induced by an externally applied electric fields. Specifically, the research seeks to determine how membrane electric potential and charge elicit membrane responses such a stretching or compression, curvature, and phase transitions, and vice versa, how changes in the membrane morphology modulate the transmembrane potential. Mathematically, these are challenging free boundary problems exhibiting complex dynamics. Continuum theory will be used to model the ions transport, motion of a charged lipid membrane interface and the surrounding liquids. A computational method is being developed to solve these complicated transient three-dimensional free-boundary problems. Limiting cases are investigated analytically, using asymptotic and perturbation methods. Experimentally, using giant unilamellar vesicles (GUVs) as a model membrane system we develop novel methodologies to probe the dynamic coupling between shape and voltage of biomembranes. The techniques are based on the flickering spectroscopy (analysis of the thermally driven micron- and sub-micron membrane undulations) and GUV deformation in applied electric fields. We will investigate membranes with broad range of compositions mimicking biological membranes. The experimental results will inform the mathematical models in terms of relevant physics and material parameters, and vice versa, the theories will provide guidance for the experiments. The GUV dynamics are visualized using optical microscopy. This supplementary proposal therefore requests funds to support the purchase of a new microscope set up to be dedicated for these studies.