Neural stimulation and modulation with sub-cellular precision by optomechanical bio-dart

IF 3.5 3区 医学 Q2 CHEMISTRY, MEDICINAL ACS Medicinal Chemistry Letters Pub Date : 2024-09-19 DOI:10.1038/s41377-024-01617-9
Guoshuai Zhu, Jianyun Xiong, Xing Li, Ziyi He, Shuhan Zhong, Junlin Chen, Yang Shi, Ting Pan, Li Zhang, Baojun Li, Hongbao Xin
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Abstract

Neural stimulation and modulation at high spatial resolution are crucial for mediating neuronal signaling and plasticity, aiding in a better understanding of neuronal dysfunction and neurodegenerative diseases. However, developing a biocompatible and precisely controllable technique for accurate and effective stimulation and modulation of neurons at the subcellular level is highly challenging. Here, we report an optomechanical method for neural stimulation and modulation with subcellular precision using optically controlled bio-darts. The bio-dart is obtained from the tip of sunflower pollen grain and can generate transient pressure on the cell membrane with submicrometer spatial resolution when propelled by optical scattering force controlled with an optical fiber probe, which results in precision neural stimulation via precisely activation of membrane mechanosensitive ion channel. Importantly, controllable modulation of a single neuronal cell, even down to subcellular neuronal structures such as dendrites, axons, and soma, can be achieved. This bio-dart can also serve as a drug delivery tool for multifunctional neural stimulation and modulation. Remarkably, our optomechanical bio-darts can also be used for in vivo neural stimulation in larval zebrafish. This strategy provides a novel approach for neural stimulation and modulation with sub-cellular precision, paving the way for high-precision neuronal plasticity and neuromodulation.

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利用光机械生物镖实现亚细胞精度的神经刺激和调节
高空间分辨率的神经刺激和调控对于介导神经元信号传导和可塑性至关重要,有助于更好地了解神经元功能障碍和神经退行性疾病。然而,开发一种生物相容性好、可精确控制的技术,在亚细胞水平对神经元进行精确有效的刺激和调控,是一项极具挑战性的工作。在此,我们报告了一种使用光控生物镖在亚细胞水平精确刺激和调节神经元的光学机械方法。这种生物镖取自向日葵花粉粒的顶端,在光纤探针控制的光散射力推动下,可在细胞膜上产生亚微米级空间分辨率的瞬时压力,从而通过精确激活膜机械敏感离子通道实现精确的神经刺激。重要的是,可以实现对单个神经元细胞的可控调制,甚至可以精确到树突、轴突和体节等亚细胞神经元结构。这种生物镖还可以作为药物输送工具,用于多功能神经刺激和调控。值得注意的是,我们的光机械生物镖还可用于对幼体斑马鱼进行体内神经刺激。这种策略为亚细胞精度的神经刺激和调控提供了一种新方法,为高精度神经元可塑性和神经调控铺平了道路。
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来源期刊
ACS Medicinal Chemistry Letters
ACS Medicinal Chemistry Letters CHEMISTRY, MEDICINAL-
CiteScore
7.30
自引率
2.40%
发文量
328
审稿时长
1 months
期刊介绍: ACS Medicinal Chemistry Letters is interested in receiving manuscripts that discuss various aspects of medicinal chemistry. The journal will publish studies that pertain to a broad range of subject matter, including compound design and optimization, biological evaluation, drug delivery, imaging agents, and pharmacology of both small and large bioactive molecules. Specific areas include but are not limited to: Identification, synthesis, and optimization of lead biologically active molecules and drugs (small molecules and biologics) Biological characterization of new molecular entities in the context of drug discovery Computational, cheminformatics, and structural studies for the identification or SAR analysis of bioactive molecules, ligands and their targets, etc. Novel and improved methodologies, including radiation biochemistry, with broad application to medicinal chemistry Discovery technologies for biologically active molecules from both synthetic and natural (plant and other) sources Pharmacokinetic/pharmacodynamic studies that address mechanisms underlying drug disposition and response Pharmacogenetic and pharmacogenomic studies used to enhance drug design and the translation of medicinal chemistry into the clinic Mechanistic drug metabolism and regulation of metabolic enzyme gene expression Chemistry patents relevant to the medicinal chemistry field.
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