Interrogating Biophysical Mechanisms of Magnetogenetic Cell Stimulation at Radio Frequencies

探究射频刺激磁发生细胞的生物物理机制

• 批准号: 10132415
• 负责人: CHUNLEI LIU
• 金额: $ 48.92万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10132415
• 关键词: Animal Model; Area; BRAIN initiative; Binding; Biophysical Process; Biophysics; Brain; Calcium; Cations; Cell Line; Cell membrane; Cells; Cellular Metabolic Process; Characteristics; Chemicals; Chimeric Proteins; Complex; Conflict (Psychology); DNA; Dependence; Electric Stimulation; Electromagnetic Fields; Electromagnetics; Energy Transfer; Family; Ferritin; Frequencies; Future; Goals; Heating; High temperature of physical object; In Situ; In Vitro; Ion Channel; Iron; Kininogens; Laws; Lipid Peroxidation; Lipids; Magnetic nanoparticles; Magnetism; Measures; Membrane; Methods; Modeling; Nature; Neuraxis; Neurobiology; Neurons; Operative Surgical Procedures; Penetration; Permeability; Physics; Physiological; Process; Proteins; Protocols documentation; Reporting; Research; Safety; Signal Pathway; Specific qualifier value; Specificity; Stimulus; System; TRPV channel; TRPV1 gene; Techniques; Technology; Temperature; Thermodynamics; Tissues; Vanilloid; Wireless Technology; base; cell type; design; experimental study; improved; in vivo; magnetic field; mechanical force; neural stimulation; novel; optogenetics; particle; peroxidation; radio frequency; receptor; response; uptake; voltage

Abstract Magnetogenetics is a recently proposed method for stimulating cells using electromagnetic fields. In one approach, radio-frequency (RF) electromagnetic fields are applied to stimulate membrane channel proteins such as TRPV1 and TRPV4 that are attached to ferritins. The concept is highly attractive as it enables wireless neural stimulation without limitation on penetration depth or the requirement of invasive surgeries. If successful, RF- based magnetogenetics can provide a non-invasive approach for large-scale neural stimulation that can reach anywhere in the brain and achieve cellular specificity. This capability overcomes a significant limitation in other techniques such as electrical stimulation and optogenetics where stimulation is spatially restricted. However, while there have been several independent reports of experimental evidences for magnetogenetic effects using RF waves, the physical and neurobiological underpinnings of such effects remain unclear and controversial. Reported experiments have been conducted only in a few selected frequencies and amplitudes and the responses were mostly measured indirectly based on downstream physiological effects. The objective of the proposed project is to systematically characterize, model and validate the neurobiological and cellular responses upon RF stimulation in neurons expressing ferritin-attached TRPV1 and TRPV4 channels. Specifically, we aim to characterize these magnetogenetic channels of their: 1) neuronal responses to electrical and chemical stimuli and to RF stimulation over a wide range of frequencies and amplitudes; 2) temperature responses to RF stimulation at the protein, cytoplasmic membrane and cellular level; 3) cellular metabolic processes upon RF stimulation. We will systematically evaluate two novel working hypotheses of the underlying mechanisms. If successful, the project will characterize the cellular responses to RF stimulation, quantify activation thresholds and safety limits, establish standard protocols and elucidate the biophysical underpinnings of this reported RF- based magnetogenetic phenomenon. It would resolve a fundamental challenge in advancing this technology and guide a more rationale design and improvement of the techniques. Understanding the mechanisms of the initial reports of magnetogenetics would be a significant addition to the present ensemble of neuro-stimulation technologies such as electrical stimulation and optogenetics and contribute to one central goal of the BRAIN Initiative that is to develop new and improved perturbation technologies suitable for controlling specified cell types and circuits to modulate function in the central nervous system.

抽象的 磁遗传学是最近提出的一种利用电磁场刺激细胞的方法。合而为一 方法，射频（RF）电磁场被用来刺激膜通道蛋白，例如 如 TRPV1 和 TRPV4 附着在铁蛋白上。这个概念非常有吸引力，因为它可以实现无线神经网络 刺激不受穿透深度或侵入性手术要求的限制。如果成功，RF- 基于磁遗传学可以为大规模神经刺激提供一种非侵入性方法，可以达到 大脑的任何地方并实现细胞特异性。此功能克服了其他方面的重大限制 电刺激和光遗传学等刺激在空间上受到限制的技术。然而， 虽然已经有几份关于磁发生效应的实验证据的独立报告， 射频波这种效应的物理和神经生物学基础仍不清楚且存在争议。 报告的实验仅在少数选定的频率和幅度下进行，并且 反应大多是根据下游生理效应间接测量的。该计划的目标 拟议的项目是系统地表征、建模和验证神经生物学和细胞反应 射频刺激表达铁蛋白附着的 TRPV1 和 TRPV4 通道的神经元。具体来说，我们的目标是 表征它们的这些磁发生通道：1）神经元对电和化学刺激的反应 以及各种频率和幅度的射频刺激； 2) 温度对射频的响应 在蛋白质、细胞质膜和细胞水平上进行刺激； 3) RF下的​​细胞代谢过程 刺激。我们将系统地评估潜在机制的两个新颖的工作假设。如果 如果成功，该项目将表征细胞对射频刺激的反应，量化激活阈值 和安全限制，建立标准协议并阐明本报告的 RF-的生物物理基础 基于磁发生现象。它将解决推进这项技术的基本挑战 指导技术更加合理的设计和改进。了解初始机制 磁遗传学的报告将是对现有神经刺激体系的重要补充 电刺激和光遗传学等技术有助于实现大脑的一个中心目标 旨在开发适合控制特定细胞的新的和改进的扰动技术的倡议 调节中枢神经系统功能的类型和电路。