Department of Biomedical Engineering and Chemical Engineering, The University of Texas at San Antonio, San Antonio, TX, 78249, USA.
Department of Physical Chemistry, University of the Basque Country UPV/EHU, Leioa, 48940, Spain.
Adv Healthc Mater. 2022 Mar;11(6):e2101826. doi: 10.1002/adhm.202101826. Epub 2021 Dec 23.
Noninvasive manipulation of cell signaling is critical in basic neuroscience research and in developing therapies for neurological disorders and psychiatric conditions. Here, the wireless force-induced stimulation of primary neuronal circuits through mechanotransduction mediated by magnetic microdiscs (MMDs) under applied low-intensity and low-frequency alternating magnetic fields (AMFs), is described. MMDs are fabricated by top-down lithography techniques that allow for cost-effective mass production of biocompatible MMDs with high saturation and zero magnetic magnetic moment at remanence. MMDs are utilized as transducers of AMFs into mechanical forces. When MMDs are exposed to primary rat neuronal circuits, their magneto-mechanical actuation triggers the response of specific mechanosensitive ion channels expressed on the cell membranes activating ≈50% of hippocampal and ≈90% of cortical neurons subjected to the treatment. Mechanotransduction is confirmed by the inhibition of mechanosensitive transmembrane channels with Gd . Mechanotransduction mediated by MMDs cause no cytotoxic effect to neuronal cultures. This technology fulfills the requirements of cell-type specificity and weak magnetic fields, two limiting factors in the development of noninvasive neuromodulation therapies and clinical equipment design. Moreover, high efficiency and long-lasting stimulations are successfully achieved. This research represents a fundamental step forward for magneto-mechanical control of neural activity using disc-shaped micromaterials with tailored magnetic properties.
非侵入性地操纵细胞信号对于基础神经科学研究以及开发神经紊乱和精神疾病的治疗方法至关重要。在这里,通过磁微盘(MMD)介导的机械转导,在施加的低强度和低频交流磁场(AMF)下,对原代神经元回路进行无线力诱导刺激。MMD 是通过自上而下的光刻技术制造的,这种技术允许以具有成本效益的方式大规模生产具有高饱和和零剩余磁矩的生物相容性 MMD。MMD 用作 AMF 到机械力的转换器。当 MMD 暴露于原代大鼠神经元回路时,它们的磁机械致动会触发细胞膜上表达的特定机械敏感离子通道的响应,从而使约 50%的海马体和约 90%的皮质神经元对处理产生反应。通过用 Gd 抑制机械敏感跨膜通道来确认机械转导。MMD 介导的机械转导对神经元培养物没有细胞毒性作用。这项技术满足了细胞类型特异性和弱磁场的要求,这是开发非侵入性神经调节治疗和临床设备设计的两个限制因素。此外,还成功实现了高效率和持久的刺激。这项研究代表了使用具有定制磁性的盘状微材料对神经活动进行磁机械控制的重要一步。