The quintessential barrier to recovery after spinal cord injury (SCI) is the limited regeneration of the central nervous system. Understanding the biochemical mediators that limit neuron regeneration is key to unlocking new therapeutics and restoring function after SCI. Our lab previously established the mechanosensitive ion channel Piezo as being an inhibitor of axon regeneration. We determined Piezo is enriched at the growth cone after injury, and its activation blocks further growth. However, the physical interactions causing Piezo channel opening remain unknown. Here we establish a framework for investigating Piezo’s role in the growth cone and propose a glia-neuron interaction that leads to its opening. We determine that neurons with Piezo channels knocked out feature much more dynamic growth cones, and that these growth cones interact with surrounding glia cells. We demonstrate that these interactions may be lipid raft dependent, and that they may be mediated by Flotilin 1 (Flot1). Continuation of this work will allow us to better understand the cell-to-cell interactions dictating axon growth after injury and will motivate new therapeutic targets.