Hybrid-nanomaterials for non-genetic optical stimulation of excitable cells

用于可兴奋细胞非遗传光刺激的混合纳米材料

• 批准号: 9979070
• 负责人: Tzahi Cohen-Karni
• 金额: $ 21.83万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-03 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9979070
• 关键词: 3-Dimensional; Address; Affect; Area; Arrhythmia; Autophagocytosis; Basic Science; Biological Assay; Brain; Breeding; Caliber; Cardiac Myocytes; Cell membrane; Cell physiology; Cells; Charge; Clinical Management; Communication; Data; Dimensions; Disease; Electric Conductivity; Electric Stimulation; Electrodes; Electrophysiology (science); Engineering; Exhibits; Future; Gene Expression; Generations; Genetic; Health; Heart; Heating; Hippocampus (Brain); Homeostasis; Hybrids; Image; In Vitro; Individual; Knowledge; Lasers; Length; Libraries; Light; Lighting; Location; Membrane; Membrane Potentials; Methods; Modification; Morphology; Neuraxis; Neurons; Optics; Organism; Organoids; Output; Pacemakers; Parkinson Disease; Peripheral Nervous System; Physiologic pulse; Play; Process; Property; Proteins; Protocols documentation; Resolution; Role; Scientist; Serotyping; Signal Transduction; Site; Structure; Surface; System; Techniques; Technology; Temperature; Therapeutic Intervention; Time; Tissue Engineering; Tissues; Translating; Viral; absorption; base; cell injury; cell type; chronic pain; clinical translation; deep brain stimulator; density; design; electrical property; energy density; gene product; graphene; in vivo; minimally invasive; mitochondrial membrane; multi-electrode arrays; nanomaterials; nanowire; nervous system disorder; neural circuit; new technology; new therapeutic target; non-genetic; novel; novel therapeutic intervention; optical imaging; optogenetics; patch clamp; physical property; response; screening; temporal measurement; tool; translation to humans; two-dimensional

Electrical stimulation of tissue and ultimately individual cells has not only played an essential role in our understanding of the structure and function of excitable tissue but continues to serve as the basis for a variety of therapeutic interventions for the treatment of disorders ranging from cardiac arrhythmias to Parkinson’s disease. Advances in technology have attempted to overcome barriers associated with the spatial resolution (i.e., who and where to stimulate) and the invasiveness of the process. Optogenetics has revolutionized the way we can record and affect the electrophysiology of cells and tissue, using light as the input/output (I/O) interface. Though optogenetics has developed at a great pace and is making profound scientific contributions, the core of the technique requires genetic modification of the cells or organism (that may affect cellular homeostasis). This presents challenges both in terms of achieving targeted gene expression and the potential deleterious consequences of the expression of foreign proteins, which have implications on clinical translation to humans and regulatory approval. Photostimulation using Au and Si-based nanomaterials has shown promise for non- genetic remote stimulation of cells, using light to trigger highly-localized heating. However, these methods still suffer from key limitations including the need for relatively high laser power due to low absorption cross-section, low thermal conversion efficiency, and unproven long-term stability. Base on the fact that transient capacitive or Faradaic currents due to either photothermal or photoelectrical effects will result with membrane depolarization (excitation) or hyperpolarization (inhibition), we propose to develop and study a breakthrough hybrid- nanomaterial synthesis process to enable minimally-invasive, remote and non-genetic light-induced control of targeted cell activity with high spatial-temporal resolution. To do so, we will combine one-dimensional (1D) nanowires (NWs) and two-dimensional (2D) graphene flakes grown out-of-plane with tailor-made physical properties for highly-controlled photostimulation through either photothermal or photoelectrical processes. Our non-genetic NW templated 3D fuzzy graphene (NT-3DFG) platform will add a powerful tool to the basic scientists studying cell signaling within and between tissues, obviating the need for slow and expensive breeding protocols and/or the screening of viral serotypes to enable the use of light to control cell activity. As we continue to struggle to understand the cells and circuits involved in health and disease, our approach to controlling cell excitability has the potential to accelerate knowledge generation as well as the identification of novel therapeutic targets. In addition to the knowledge generated, this technology should replace the current wire electrode-based approaches for the treatment of diseases ranging from chronic pain to Parkinson’s disease. Last, this platform can be adapted to address challenges in tissue engineering, i.e. the much-needed non-genetic stimulation control of engineered tissues. By controlled delivery of the NT-3DFG we will be able to locally and selectively control cellular activity with high spatial and temporal resolution of 3D tissues.

组织和最终单个细胞的电气模拟不仅在我们的 了解令人兴奋的组织的结构和功能，但继续作为多样性的基础 治疗从心律不齐到帕金森氏症的疾病治疗的治疗干预措施 疾病。技术的进步试图克服与空间分辨率相关的障碍 （即，谁和在哪里刺激）以及该过程的侵入性。光遗传学彻底改变了方式 我们可以使用光作为输入/输出（I/O）界面来记录和影响细胞和组织的电生理学。 尽管光遗传学已经以很大的速度发展，并且正在做出深刻的科学贡献，但 该技术需要对细胞或生物体的遗传修饰（可能影响细胞稳态）。这 在实现靶向基因表达和潜在有害的方面提出了挑战 外蛋白表达的后果，对人类的临床翻译具有影响 和法规批准。使用基于AU和Si的纳米材料进行光刺激已显示出对非 - 遗传远程刺激细胞，使用光触发高度定位的加热。但是，这些方法仍然 受到关键局限性，包括由于低抽象横截面而需要相对较高的激光功率， 低热转化效率和未经证实的长期稳定性。基于瞬态电容或 由于光热或光电效应引起的法拉达电流将导致膜去极化 （激发）或超极化（抑制），我们建议开发和研究突破性的杂种 纳米材料合成过程，以实现对最小侵入性，远程和非遗传光诱导的控制 具有高时空分辨率的靶向细胞活性。为此，我们将结合一维（1D） 纳米线（NWS）和二维（2D）石墨烯薄片，其平面外生长，并用量身定制的物理 通过光热过程或光电过程进行高度控制的光刺激的性能。我们的 非基因NW模板3D模糊石墨烯（NT-3DFG）平台将为基本科学家添加强大的工具 研究组织内部和组织之间的细胞信号传导，从而消除了对缓慢且昂贵的繁殖方案的需求 和/或筛选病毒血清型，以使光使用光细胞活性。随着我们继续挣扎 为了了解健康和疾病所涉及的细胞和电路，我们控制细胞兴奋性的方法 有可能加速知识产生以及新型治疗靶标的识别。在 除了产生的知识之外，该技术应替换当前的基于电线电极 治疗从慢性疼痛到帕金森氏病等疾病的方法。最后，这个平台 可以适应组织工程的挑战，即急需的非遗传模拟 控制工程组织。通过控制NT-3DFG的传递，我们将能够在本地和选择性地进行 控制3D组织的高空间和临时分辨率的细胞活性。