Intra-axonal Nanomagnetic Forces Differentially Impact hTau40 Transport Dynamics in Primary Cortical and Hippocampal Neurons

A crucial aspect of neural engineering is the ability to manipulate proteins that are substantially involved in axonal outgrowth and maintenance. Previous work in this field has shown that applying low-magnitude (piconewton) forces to early stage neurons can result in altered distributions of critical structural proteins, such as the microtubule-associated protein Tau. Uncovering the mechanisms of Tau redistribution could provide a tool for manipulating dysregulated forms of the protein. This study examined how the transport of Tau responded to intra-axonal nanomagnetic forces (NMFs) in primary cortical and hippocampal neurons. High magnification, live cell fluorescent imaging was employed to visualize the transport of both full-length human Tau (hTau40) and amine-terminated, starch-coated fluorescent magnetic nanoparticles (afMNPs) to observe how these cell-internal forces could impact the transport of hTau40 within the axon. Here, we found that afMNPs acted by pulling on hTau40 puncta under NMF application, especially within cortical cells, where afMNPs were more likely to be found within the axon. Forces greater than 1 pN enabled differentiated transport speeds and displacement of hTau40 based on relative force direction. This data indicates that NMF can be utilized to engineer hTau40 transport, even in cells at later stages of maturation.