Piconewton Mechanical Forces Promote Neurite Growth

Abstract

Investigations over half a century have indicated that mechanical forces induce neurite growth, with neurites elongating at a rate of 0.1–0.3 μm h−1 pN−1 when mechanical force exceeds a threshold, with this being identified as 400–1000 pN for neurites of PC12 cells. In this article, we demonstrate that neurite elongation of PC12 cells 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.

Manipulation of Axonal Outgrowth via Exogenous Low Forces

“…Recent studies have contradicted this conclusion, pointing out that there is no threshold for elongation. Neurites of PC12 cells or hippocampal neurons stretched with forces in the range of 1-10 pN increased their length from 50 to 100% compared to the condition of spontaneous elongation, in 48 h [78,79]. Interestingly, the elongation rate was very similar to the one calculated in previous studies (0.1-1 µm h −1 pN −1 ) [61], although the applied force was five orders of magnitude lower than that used in previous work.…”

“…Interestingly, the elongation rate was very similar to the one calculated in previous studies (0.1-1 µm h −1 pN −1 ) [61], although the applied force was five orders of magnitude lower than that used in previous work. A possible explanation for this discrepancy is that axons respond to extremely low forces acting for days as viscoelastic fluid, while neurites show an elastic behavior when subjected to intense forces acting for a shorter time [79]. Indeed, a similar result was obtained by Abraham et al investigating the response of primary cortical neurons to cyclic strain over hours with physiologically relevant amplitudes and repeated frequencies [80].…”

“…Only the axial component oriented from the axon hillock to the tip is productive for stretchgrowth [79]. Stretch-growth requires continuous loading, and, within a few minutes after force removal, neurites resume the behavior of tip-growth [79,82].…”

Parallelized manipulation of adherent living cells by magnetic nanoparticles-mediated forces

“…MNPs, as force-mediating objects, can manipulate cell structures either inside the cytosol or outside of the cell via the cell membrane. Previous studies have used them with success to manipulate directional motility of cells (Tseng et al 2012;Bradshaw et al 2014;White et al 2015;Alon et al 2015;Xia et al 2016) or neurite elongation, either associated to cell outer membrane (Fass and Odde 2003) or inside the cells, either packed into endosomes, or as free particles in the cytosol (Kunze et al 2015;Riggio et al 2014;Raffa et al 2018;Marcus et al 2016).…”

Recent Advances in The Use of Magnetic Nanoparticles to Promote Neuroregeneration

“…In this context, MNPs have ability to manipulate axonal growth and guidance. Interestingly, by labeling neurites with MNPs, the extremely low forces generated by MNPs under the effect of the external magnetic field can be used for stretching the neurites, resulting in elongation and growth by a mechanism known as 'stretch growth' [5]. MNP-driven forces can be also used to gain control on axonal guidance, by orientating the direction of growth of neurites [6].…”