The Interplay of Electric Potential and Morphology of Biomembranes - Supplement

生物膜电势与形态的相互作用 - 补充

• 批准号: 10581416
• 负责人: Petia M Vlahovska
• 金额: $ 11.27万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-05 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10581416
• 关键词: 3-Dimensional; Action Potentials; Biological; Biomimetics; Brain; Cell Communication; Cell membrane; Cells; Charge; Complex; Computing Methodologies; Coupling; Development; Electricity; Embryonic Development; Exhibits; Funding; Generations; Hodgkin-Huxley model; Ion Channel; Ion Transport; Liquid substance; Mathematics; Mechanics; Membrane; Membrane Lipids; Membrane Microdomains; Membrane Potentials; Methodology; Methods; Microscope; Microscopy; Modeling; Morphology; Motion; Muscle Cells; Neurons; Optics; Phase Transition; Physics; Play; Research; Role; Shapes; Signal Transduction; Spectrum Analysis; Stimulus; Stress; Stretching; System; Techniques; base; bioelectricity; cell behavior; electric field; electrical potential; experimental study; healing; insight; mathematical model; membrane model; migration; novel; novel therapeutic intervention; response; submicron; theories; tumor progression; unilamellar vesicle; voltage

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.

总结 跨质膜的电势差对于所有活细胞是共同的，并且对于细胞的生长至关重要。 产生细胞间通讯的动作电位。除了兴奋的神经和肌肉细胞， 与跨膜电位结合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、伤口愈合和癌症进展中起关键作用。 细胞对电刺激的反应机制在很大程度上是未知的。以电力为中心的观点， 以Hodgkin-Huxley模型为代表，重点关注电压依赖性离子通道。但近几 多年来，膜力学正在成为一个潜在的重要角色：膜变形是 检测到与动作电位共同传播，已经发现几种离子通道都是电压- 门控的和机械敏感的以及脂筏被认为是电传感器。评估 生物电现象中这些膜相关效应的相关性需要对以下方面有基本的了解： 膜形态、应力和电压之间的耦合是有限的。 为了填补这一空白，本文采用理论与实验相结合的方法对仿生材料进行了研究 膜具有由外部施加的电场诱导的跨膜电位。具体而言是 研究试图确定膜电势和电荷如何引起膜响应， 拉伸或压缩，曲率和相变，反之亦然，如何在膜的变化 形态学调节跨膜电位。从数学上讲，这些都是具有挑战性的自由边界 表现出复杂动态的问题。连续介质理论将被用来模拟离子的传输，运动， 带电荷的脂质膜界面和周围的液体。正在开发一种计算方法， 解决这些复杂的瞬态三维自由边界问题。对限制性案件进行调查 分析，使用渐近和扰动方法。实验上，使用巨大的单层囊泡 作为一个模型膜系统，我们开发了新的方法来探测动态耦合 生物膜的形状和电压之间的关系。该技术是基于闪烁光谱 （热驱动的微米和亚微米膜起伏的分析）和GUV变形， 外加电场我们将研究具有广泛组成的膜， 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。 使用光学显微镜的GUV动力学可视化。因此，本补充建议 要求提供资金，以支持购买专门用于这些研究的新显微镜。