Controlling and Organizing Neuronal Networks using Magnetic Manipulations

Ganit Indech 1,2 Michal Marcus 2,3 Naor Vardi 1,2 Alehandra Smith 2,3 Amos Sharoni 1,2 Orit Shefi 2,3
1Bar Ilan University, Israel
2Bar Ilan University, Israel
3Bar Ilan University, Israel

Guiding neuronal migration and outgrowth has great importance for therapeutic applications and for bioelectronics interfaces. Many efforts have been devoted to the development of tools to form predesigned structured neuronal networks. Here a unique approach is proposed to localize cell bodies and direct neurite outgrowth via local magnetic manipulations. Inspired by spintronic devices, photolithography and sputter-deposition are used to fabricate micro-patterned magnetic substrates with controllable magnetization orientation with perpendicular magnetization, which provide stable attraction forces along the entire magnetic pads. Atop the device, magnetized PC12 cells are plated and differentiated. The cells are transformed to magnetic units by incubating them with superparamagnetic nanoparticles prior to plating. Compared to substrate with topographical cues, which showed partial response to the topographic effect of line–patterned ridges with hundreds of micrometers height, the majority of MNPs-loaded cells adhere to the magnetic pads and show high affinity to the magnetic patterns. In addition, analyzing neuronal growth with time shows that the magnetic device also affects the directionality of the extending neurites to align with the electrodes. Micro-magnetic simulations demonstrate that perpendicularly magnetized electrodes are much more efficient in plating cells and provide explanation why the neurites grow atop the electrodes in this case. Our approach enables the design of complex micro-patterned geometries, which can be used to control and manipulate the formation of neural networks grown on those substrates. The ability to remotely control neuronal motility together with network design via smart magnetic materials opens possibilities for new neuronal interfaces and implanted therapeutic devices.

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