Department of Bioengineering, University of California, Los Angeles, California 90095, USA.
Lab Chip. 2017 Feb 28;17(5):842-854. doi: 10.1039/c6lc01349j.
Vesicle transport is a major underlying mechanism of cell communication. Inhibiting vesicle transport in brain cells results in blockage of neuronal signals, even in intact neuronal networks. Modulating intracellular vesicle transport can have a huge impact on the development of new neurotherapeutic concepts, but only if we can specifically interfere with intracellular transport patterns. Here, we propose to modulate motion of intracellular lipid vesicles in rat cortical neurons based on exogenously bioconjugated and cell internalized superparamagnetic iron oxide nanoparticles (SPIONs) within microengineered magnetic gradients on-chip. Upon application of 6-126 pN on intracellular vesicles in neuronal cells, we explored how the magnetic force stimulus impacts the motion pattern of vesicles at various intracellular locations without modulating the entire cell morphology. Altering vesicle dynamics was quantified using, mean square displacement, a caging diameter and the total traveled distance. We observed a de-acceleration of intercellular vesicle motility, while applying nanomagnetic forces to cultured neurons with SPIONs, which can be explained by a decrease in motility due to opposing magnetic force direction. Ultimately, using nanomagnetic forces inside neurons may permit us to stop the mis-sorting of intracellular organelles, proteins and cell signals, which have been associated with cellular dysfunction. Furthermore, nanomagnetic force applications will allow us to wirelessly guide axons and dendrites by exogenously using permanent magnetic field gradients.
囊泡运输是细胞通讯的主要潜在机制。抑制脑细胞中的囊泡运输会导致神经元信号阻断,即使在完整的神经元网络中也是如此。调节细胞内囊泡运输可以对新的神经治疗概念的发展产生巨大影响,但前提是我们能够特异性地干扰细胞内运输模式。在这里,我们提出基于在微工程化的磁梯度芯片上的细胞内化超顺磁氧化铁纳米粒子(SPION)的外源性生物共轭物来调节大鼠皮质神经元内细胞内脂质囊泡的运动。在对神经元细胞内的细胞内囊泡施加 6-126 pN 的力时,我们探索了在不调节整个细胞形态的情况下,磁场刺激如何影响各种细胞内位置处囊泡的运动模式。使用均方根位移、笼状直径和总行进距离来量化囊泡动力学的变化。我们观察到,当用 SPION 对培养神经元施加纳米磁力时,细胞间囊泡的运动性会减速,这可以通过由于相反的磁力方向导致运动性降低来解释。最终,在神经元内使用纳米磁力可能使我们能够阻止细胞内细胞器、蛋白质和细胞信号的错误分拣,这些与细胞功能障碍有关。此外,纳米磁力的应用将使我们能够通过外部施加的永久磁场梯度无线引导轴突和树突。
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