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.

对组织和最终单个细胞的电刺激不仅在我们的 对可兴奋组织的结构和功能的了解，但仍是各种组织的基础 治疗从心律失常到帕金森氏症的各种疾病的治疗干预 疾病。技术的进步试图克服与空间分辨率相关的障碍 (即，刺激谁和在哪里)以及这一过程的侵入性。光遗传学已经彻底改变了 我们可以记录和影响细胞和组织的电生理，使用光作为输入/输出(I/O)接口。 虽然光遗传学发展很快，做出了深刻的科学贡献，但其核心是 这项技术需要对细胞或有机体进行基因改造(这可能会影响细胞的动态平衡)。这 在实现有针对性的基因表达和潜在的有害因素方面都存在挑战 外源蛋白表达的后果，这对临床向人类的翻译有影响 以及监管部门的批准。使用金和硅基纳米材料的光刺激技术在非 基因远程刺激细胞，使用光来触发高度局域的加热。然而，这些方法仍然 受到关键限制，包括由于低吸收截面而需要相对较高的激光功率， 热转换效率低，长期稳定性未经证实。基于这样一个事实，即瞬时电容或 膜去极化时，由于光热或光电效应而产生的法拉第电流 (激发)或超极化(抑制)，我们建议开发和研究一种突破性的杂交-- 纳米材料合成工艺，实现微创、远程和非遗传光诱导控制 具有高时空分辨率的靶向细胞活动。为此，我们将结合一维(1D) 纳米线(NW)和二维(2D)石墨烯薄片通过量身定做的物理方法进行平面外生长 通过光热或光电过程实现高度可控的光刺激特性。我们的 非遗传NW模板化3D模糊石墨烯(NT-3DFG)平台将为基础科学家增加一个强大的工具 研究组织内和组织间的细胞信号，消除了对缓慢和昂贵的育种方案的需要 和/或筛选病毒血清型，以便能够使用光来控制细胞活动。当我们继续奋斗的时候 为了了解与健康和疾病有关的细胞和回路，我们控制细胞兴奋性的方法 具有加速知识生成以及确定新的治疗靶点的潜力。在……里面 除了产生的知识外，这项技术应该取代目前的焊丝电极为主 治疗从慢性疼痛到帕金森氏症的各种疾病的方法。最后，这个平台 可以用来应对组织工程中的挑战，即急需的非遗传刺激 对工程组织的控制。通过NT-3DFG的受控交付，我们将能够局部和选择性地 通过3D组织的高空间和时间分辨率控制细胞活动。