Force induces axon growth in inhibitory conditions

Abstract

Axon navigation is guided by spatial patterns of chemical and physical cues in the developing central nervous system. Following injury, these patterns are disrupted, the microenvironment evolves rapidly, and inhibitory molecules create a barrier to the regeneration of severed axons. We have recently developed a technology called nano-pulling designed to stimulate axon growth and regeneration by modulating neuronal mechanotransduction. In this paper, we demonstrate that nano-pulling can induce axon growth in hippocampal neurons even in the presence of repulsive cues, such as chondroitin sulfate proteoglycans, semaphorin 3A, microglial activation, and pro-inflammatory cytokines. Nano-pulling can also enhance the elongation of neural processes in neural progenitors transplanted into an organotypic spinal cord injury model that mimics the tissue complexity and inflammation seen in in vivo models. Our data suggest that nano-pulling could be used as a strategy to manipulate axon growth, overcoming certain extrinsic inhibitory factors.