The Interplay of Electric Potential and Morphology of Biomembranes

生物膜电势与形态的相互作用

• 批准号: 10254345
• 负责人: Petia M Vlahovska
• 金额: $ 30.68万
• 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/10254345
• 关键词: 3-Dimensional; Action Potentials; Biological; Biomimetics; Brain; Cell Communication; Cell membrane; Cells; Charge; Complex; Computing Methodologies; Coupling; Electricity; Embryonic Development; Exhibits; Generations; Health; Hodgkin-Huxley model; Human; Instruction; Ion Channel; Ion Transport; Liquid substance; Mathematics; Mechanics; Membrane; Membrane Lipids; Membrane Microdomains; Membrane Potentials; Methodology; Modeling; Morphology; Motion; Muscle; Nerve; Outcome; Phase Transition; Physics; Play; Research; Rest; Role; Shapes; Signal Transduction; Spectrum Analysis; Stimulus; Stress; Stretching; System; Techniques; Theoretical Studies; base; bioelectricity; cancer therapy; cell behavior; electric field; electrical potential; experimental study; healing; mathematical model; membrane model; migration; neuronal excitability; new therapeutic target; novel; novel therapeutics; response; submicron; theories; tumor progression; unilamellar vesicle; virtual; voltage; wound healing

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, 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 virtually unknown. An electricitycentered 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, the team proposes a combined theoretical and experimental study of biomimetic membranes with transmembrane potential induced by an externally applied electric fields. Specifically, the project seeks to determine how an electric potential elicits 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 proposed to solve these complicated transient three-dimensional free-boundary problems. Experimentally, using giant unilamellar vesicles (GUVs) as a model membrane system the PI will develop novel methodologies to probe the dynamic coupling between shape and voltage of biomembranes. The techniques will be based on the flickering spectroscopy (analysis of the thermally driven micron- and sub-micron membrane undulations) and GUV deformation in applied electric fields. Membranes with broad range of compositions mimicking biological membranes will be investigated. The experimental results will inform the mathematical models in terms of relevant physics and material parameters, and vice versa, the theories will guide the experiments.

跨质膜的电势差对所有活细胞都是常见的，并且对 细胞间通讯的动作电位的产生。在兴奋的神经和肌肉之外， 与跨膜电位共轭的生物电信号控制着许多细胞行为，如 迁移、定向和增殖，在胚胎发育中起着关键作用，会愈合和癌症 进步。细胞对电刺激的反应机制几乎是未知的。以Hodgkin-Huxley模型为代表的以电子为中心的观点聚焦于电压相关的离子通道。 然而，近年来，膜力学正在成为一个潜在的重要参与者：膜 形变被检测到与动作电位共同传播，已发现几个离子通道 既是电压门控的，又是机械敏感的，脂筏被认为是电子传感器。 评估这些膜相关效应在生物电现象中的相关性需要 对膜形态、应力和电压之间的耦合有基本的了解，这是 有限的。 为了填补这一空白，该团队提出了一项仿生学的理论和实验相结合的研究 在外加电场作用下产生跨膜电位的膜。具体地说， 该项目试图确定电势如何引起薄膜响应，如拉伸或 压缩、曲率和相变，反之亦然，膜的形态如何变化 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问题 表现出复杂的动态。连续介质理论将被用来模拟带电离子的输运、运动 脂膜与周围液体的界面。提出了一种求解这些问题的计算方法 复杂的瞬变三维自由边界问题。实验中，使用巨大的单层膜 囊泡(GUV)作为一种模型膜系统，PI将发展新的方法学来探索动力学 生物膜的形状和电压之间的耦合。这些技术将基于闪烁 光谱学(热驱动微米和亚微米薄膜波动的分析)和GUV 外加电场中的变形。具有广泛组成范围的模拟生物膜 将对膜进行研究。实验结果将为数学模型提供如下方面的信息 相关的物理和材料参数，反之亦然，这些理论将指导实验。