Controlling Cell Signaling via Calcium Influx Modulation Using Magnetic Nanoparticles and Alternating Magnetic Fields

Functionalized magnetic nanoparticles (MNPs) with diameter of 20-22 nm, dissipate heat when exposed to alternating magnetic fields (AMFs). This heat can be exploited to activate cells that have thermally sensitive ion channels on their membrane. One example for such ion channel is the transient receptor potential vanilliod 1 (TRPV1), non-selective cation channel that is calcium-permeable and can be activated by capsaicin, heat &gt;42 ⁰C and pH &lt; 5.9. Previous studies have demonstrated the expression of TRPV1 in various peripheral organs as well as sensory neurons. AMF has high penetration rate (&lt;10 cm) with no deleterious effects, therefore AMF is suitable for the activation of cells within deep organs in the body.<br/>We will present two examples for the use of the magnetothermal approach to trigger cell signaling. The first is magnetically-controlled hormone release from adrenal glands, demonstrated in cell cultures and in vivo. We show that injections of MNPs into the adrenal glands of genetically-intact rats are sufficient to enable magnetothermal control of calcium influx into the cells of adrenal cortex and medulla, providing means to triggering of release of adrenal stress hormones – corticosterone and epinephrine.¹ Abnormal regulation of hormones produced within the adrenal gland have been linked to altered stress responses, therefore suggesting that our magnetothermal approach can pave way towards greater understanding of the involvement of hormones in psychiatric and mental disorders. The second example is the magnetothermal control of axonal growth via enhanced calcium influx in a model of sensory nerve regeneration. In this work, we employ sensory neuronal structures dorsal root ganglia (DRGs) explants and subject them to magnetothermal stimulation mediated by AMFs in the presence of MNPs. We then quantify the effects of magnetothermal stimulation on the dynamic neurite growth in DRGs at different time points post-stimulation. Nociceptive sensory neurons and central nervous system neurons have poor regeneration capabilities. Using the magnetothermal approach to guide axonal growth suggests a new mechanistic strategy to overcome the limited axonal regeneration.<br/>¹Rosenfeld et al., Science Advances 2020