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.

跨质膜的电势差对于所有活细胞来说都是常见的，并且对于 产生细胞间通讯的动作电位。除了兴奋的神经和肌肉之外， 与跨膜电位结合的生物电信号控制许多细胞行为，例如 迁移、定向和增殖在胚胎发生、愈合和癌症中起着至关重要的作用 进展。细胞对电刺激的反应机制实际上是未知的。以霍奇金-赫胥黎模型为代表的以电为中心的观点侧重于电压依赖性离子通道。 然而，近年来，膜力学正在成为一个潜在的重要参与者：膜 检测到变形与动作电位共同传播，已发现多个离子通道 既是电压门控又是机械敏感的，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 对膜形态、应力和电压之间耦合的基本理解 有限的。 为了填补这一空白，该团队提出了仿生学的理论和实验相结合的研究 具有由外部施加的电场引起的跨膜电位的膜。具体来说， 该项目旨在确定电势如何引起膜响应，例如拉伸或 压缩、曲率和相变，反之亦然，膜形态如何变化 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。连续介质理论将用于模拟离子传输、带电粒子的运动 脂质膜与周围液体的界面。提出了一种计算方法来解决这些问题 复杂的瞬态三维自由边界问题。实验上，使用巨型单层 囊泡（GUV）作为模型膜系统，PI 将开发新的方法来探测动态 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（热驱动微米和亚微米膜波动分析）和 GUV 施加电场中的变形。具有多种模拟生物成分的膜 膜将被研究。实验结果将为数学模型提供以下信息： 相关的物理和材料参数，反之亦然，理论将指导实验。