Mechanotrasnduction of axonal growth: effects of pN forces

Although the exact mechanisms involved in the growth of axons is still incompletely understood, it is clear that force is a crucial factor for both axonal guidance and lengthening. Experimental studies indicate that forces, when carefully controlled, act as powerful stimulators of axonal lengthening. Axonal elongation as a function of the applied tensile force has been investigated by several teams. It has been found that neurites start to elongate when the applied tension is above 1 nN [1]. Recently, we established a novel approach for the application of a controlled tensile force to neurons and axons in order to accelerate regeneration after peripheral nerve injury [2]. The approach we proposed is based on the use of superparamagnetic iron oxide magnetic nanoparticles (MNP). This methodology has been used to explore the effect of pico-Newton force on axon guidance and lengthening. In contrast with previous results, we found that there is no threshold for stretched growth and we observed an elongation rate of 0.2-0.3 µm/h/pN (the same elongation rate previously reported for both central and peripheral nervous system [1]), even with the application of picoNewton forces. This finding supports the concept of “stretch growth model" of axonal growth, according to which axonal elongation is driven by tension, irrespective of its origin, i.e., from the traction exerted by the growth cone, the mass body growth or external force application.