Engineering cortical neuron polarity with nanomagnets on a chip

Area of Science:

• Neuroscience
• Biophysics
• Cell Biology

Background:

• Cell polarity is crucial for developing functional tissues and organs, with misoriented neurons causing neurological disorders.
• Mechanical stimuli, including external forces and intracellular signals, influence nervous system development and axonal outgrowth.
• The precise role of mechanical signals in single-cell polarity remains incompletely understood.

Purpose of the Study:

• To investigate the impact of precisely controlled mechanical forces on neuronal polarity and intracellular organization.
• To quantify the effects of nanoparticle-mediated forces on the neuronal cytoskeleton, specifically tau protein distribution.
• To explore the potential for mechanical manipulation of neural networks and development of neurotherapeutics.

Main Methods:

• Utilized a chip-based system with highly parallelized nanomagnets to apply local mechanical stimuli to cortical neurons.
• Quantified the effect of nanoparticle-mediated forces on intracellular tau distribution, independent of nanoparticle uptake.
• Applied forces ranging from picoNewtons (pN) to hundreds of pN to single neurons and cell clusters.

Main Results:

• Forces between 4.5-70 pN induced tau distribution in single neurons that opposed surface pattern cues.
• In cell clusters, forces of 190-270 pN caused tau repositioning.
• Cell displacement directed by magnetic fields was observed at forces exceeding 300 pN.

Conclusions:

• Mechanical forces can override surface cues in directing tau distribution in neurons.
• Specific force ranges can induce cytoskeletal changes and cell displacement in neural networks.
• Findings support the development of mechanical encoding for neural networks and novel neurotherapeutic strategies.