Mechanotransduction of axonal growth: a new strategy based on magnetic nanoparticle to promote nerve regeneration

Vittoria Raffa

Università di Pisa, Department of Biology, Pisa, Italy

Axonal growth is a complex mechanism and, recently, it has been elucidated that mechanical forces play an important role. The so-called “stretch-growth model” has been proposed as an alternative to the more widely recognized “tip-growth model”. According to the “stretch-growth model” elongation is induced by mechanical stimuli, whether these come from the growth cone, or originate from different stimuli such as body growth or the use of exogenous mechanical forces. However, this model is not yet accepted as a universal model of axonal growth, because some contradictions have emerged. The main one consists in the fact that some literature has highlighted the presence of a threshold value to overcome so that the mechanical force can stimulate the elongation of the axon. Nevertheless, this threshold value is higher than the tension generated at the growth cone and this is why it has been questioned if the “stretch growth model” is valid in physiological conditions. However, the tools previously used to investigate the effects of mechanical stress had limits regarding sensitivity and reliability, which makes them unusable to study tensions below 100 pN. To overcome this problem, we have labelled neuron-like cells and primary neurons by magnetic nanoparticles for the generation of a weak force, which may vary, under the action of an external magnetic field, from 0.1 to 10 pN. We demonstrate that neurite elongation proceeds at the same previously identified rate, on application of mechanical tension of ~ 1 pN, which is significantly lower than the force generated in-vivo by axons and growth cones. This observation raises the possibility that mechanical tension may act as an endogenous signal used by neurons for promoting neurite elongation.