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.

高空间分辨率的神经刺激和调制对于介导神经元信号传导和可塑性至关重要，有助于更好地理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和精确可控的技术来在亚细胞水平上准确有效地刺激和调节神经元是非常具有挑战性的。在这里，我们报告了一种使用光控生物飞镖进行亚细胞精度神经刺激和调节的光机械方法。该生物飞镖取自向日葵花粉粒的尖端，当由光纤探针控制的光学散射力推动时，可以在细胞膜上产生亚微米空间分辨率的瞬态压力，从而通过精确激活膜来产生精确的神经刺激机械敏感离子通道。重要的是，可以实现对单个神经元细胞的可控调节，甚至可以控制亚细胞神经元结构，如树突、轴突和体细胞。这种生物飞镖还可以作为多功能神经刺激和调节的药物输送工具。值得注意的是，我们的光机械生物飞镖也可用于斑马鱼幼虫的体内神经刺激。该策略为亚细胞精度的神经刺激和调节提供了一种新方法，为高精度神经元可塑性和神经调节铺平了道路。