UC San Diego

Peripheral nerves span one or more articulating joints, and must accommodate mechanical loads during day-to-day activities. Axons are protected in part by their undulation within the nerve, implied by the Bands of Fontana. In addition, previous studies have identified regions of increased epineurial strain and compliance, particularly near joints. Most of these studies have focused on regional differences in epineurial strain; however, how internal nerve compartments, including the axons, perceive this increased deformation is less understood. Using transgenic mice expressing a fluorescent reporter within their neurons, we tested 1) whether mesoneurial tissue contributes to regional variability in epineurial strain, and 2) whether nerves

increase their local axonal undulation in regions of high epineurial strain, as a strategy to protect nerve fibers from strain-induced damage.

In our results, we observed a decoupling between regions of high epineurial strain and high axonal tortuosity. Consistent with previous studies, decompression resulted in significant differences in regional strain, confirming strong mesoneurial influences on epineurial strain. However, regional differences in axonal tortuosity were largely unchanged by decompression or excision, signaling that epineurial measurements may not fully represent the response of the inner nerve. Based on our findings and previous literatures, we propose a neuromechanical model that permits axons to unravel along their length due to looser coupling between the peri/endoneurium. This capability may result in enhanced axonal protection to injury than suspected. These findings have implications for our understanding of nerve biomechanics as well as the progression of nerve dysfunction due to injury, disease, or surgery.