Magnetothermal Modulation of Calcium-Dependent Nerve Growth

摘要

Nerve injuries are common, and the available treatments including invasivesurgeries do not guarantee complete regeneration of the injured nerves andrestoration of function. Despite the ability of peripheral nerves to regenerate,the slow rate of axonal growth hampers the functional recovery. Developmentof new approaches to discover underlying mechanisms that may accelerateaxonal growth is needed to overcome these limitations and augment availabletreatments of nerve injury. In addition to chemical factors, recent studiessuggested the use of optogenetics and electrical stimulation to promoteaxonal growth. The underlying mechanisms of these approaches, however,require further investigation. Furthermore, their application relies on invasivehardware, which may not be compatible with injured nerves under significantmechanical deformation. Here, it is shown that thermal activation of a heatsensitive ion channel TRPV1 promotes axonal growth in a calcium-dependentmanner. By leveraging heat dissipation of magnetic nanoparticles in alternatingmagnetic fields, the calcium influx through TRPV1 channels endogenouslyexpressed in dorsal root ganglion explants is triggered remotely.The accelerated axonal growth through elongation of neurofilaments andincreased Schwann cell migration following magnetothermal stimulationis observed. These findings suggest future applications of magnetothermalmodulation of axonal growth as a minimally invasive approach to acceleratenerve regeneration.