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.

概括 质膜上的电势差对于所有活细胞都是共同的，对于 生成细胞之间通信的动作电位。超越了神经和肌肉细胞， 与跨膜电位控制的生物电信号许多细胞行为，例如迁移， 在胚胎发生中起着至关重要的作用的取向和增殖将愈合和癌症进展。 细胞对电刺激的反应的机制在很大程度上未知。以电力为中心的视图， 由Hodgkin-Huxley模型表现出来，重点是依赖电压的离子通道。但是，最近 年膜力学正在成为潜在的重要参与者：膜变形是 检测到与动作电位共汇总，已经发现几个离子通道都是电压 - 门控和机械敏感性，脂质筏已被视为电传感器。评估 这些与膜相关作用在生物电现象中的相关性需要对 有限的膜形态，应力和电压之间的耦合。 为了填补这一空白，我们采用一种合并的理论和实验方法来研究仿生 具有外部施加的电场引起的具有跨膜电势的膜。具体来说， 研究旨在确定膜电位和电荷如何引起膜反应 拉伸或压缩，曲率和相变，反之亦然，膜的变化如何变化 形态调节跨膜电位。从数学上讲，这些都在挑战自由边界 表现出复杂动态的问题。连续理论将用于建模离子传输，运动的运动 带电的脂质膜界面和周围液体。正在开发一种计算方法 解决这些复杂的瞬态三维自由界问题。研究限制案件 在分析上，使用渐近和扰动方法。实验，使用巨大的单层囊泡 （GUV）作为模型膜系统，我们开发了新的方法来探测动态耦合 在生物膜的形状和电压之间。这些技术基于闪烁的光谱法 （分析热驱动的微米和亚微米膜的外观）和GUV变形 应用的电场。我们将研究模仿生物学的各种成分的膜 膜。实验结果将以相关物理学和 物质参数，反之亦然，这些理论将为实验提供指导。 使用光学显微镜可视化GUV动力学。因此，该补充提议 要求资金支持购买新的显微镜，以专门用于这些研究。