Probing multi-scale mechanics of peripheral nerve collagen and myelin by X-ray diffraction.

Fabio Bianchi,Hua Ye,Andrew J Smith,Felix Hofmann,Mark S Thompson

doi:10.1016/j.jmbbm.2018.07.030

Abstract

Peripheral nerves are continuously subjected to mechanical forces, both during everyday movement and as a result of traumatic events. Current mechanical models focus on explaining the macroscopic behaviour of the tissue, but do not investigate how tissue strain translates to deformations at the microstructural level. Predicting the effect of macro-scale loading can help explain changes in nerve function and suggest new strategies for prevention and therapy. The aim of this study was to determine the relationship between macroscopic tensile loading and micro scale deformation in structures thought to be mechanically active in peripheral nerves: the myelin sheath enveloping axons, and axially aligned epineurial collagen fibrils. The microstructure was probed using X-ray diffraction during in situ tensile loading, measuring the micro-scale deformation in collagen and myelin, combined with high definition macroscopic video extensiometry. At a tissue level, tensile loading elongates nerves axially, whilst simultaneously compressing circumferentially. The non-linear behaviour observed in both directions is evidence, circumferentially, that the nerve core components have the ability to rearrange before bearing load and axially, of a recruitment process in epineurial collagen. At the molecular level, axially aligned epineurial collagen fibrils are strained, whilst the myelin sheath enveloping axons is compressed circumferentially. During induced compression, the myelin sheath shows high circumferential stiffness, indicating a possible role in mechanical protection of axons. The myelin sheath is deformed from low loads, despite the non-linearity of whole tissue compression, indicating more than one mechanism contributing to myelin compression. Epineurial collagen shows similar load-bearing characteristics to those of other collagenous connective tissues. This new microstructural knowledge is key to understand peripheral nerve mechanical behaviour, and will support new regenerative strategies for traumatic and repetitive injury.

Highlights

Peripheral nerves are continuously subjected to mechanical forces, elongation, and compression during everyday movement, without suffering functional losses and damage
The same slope ratio is 10 (Fig. 6a), indicating that collagen bears a higher proportion of axial load than the proportion of circumferential compression borne by myelin
We probe the micro-mechanical behaviour of peripheral nerve collagen and myelin during in situ tensile loading, by X-ray diffraction

Summary

Introduction

Peripheral nerves are continuously subjected to mechanical forces, elongation, and compression during everyday movement, without suffering functional losses and damage. Erb's palsy, caused by excessive stretching of infant heads and arms during birth, induces loss of sensation and abnormal motor function in. Mechanical tension has been proposed as a regenerative method, with mild stretch inducing axonal and whole-nerve elongation and growth, the multi-scale effects of this elongation have not been studied (Pfister et al, 2004; Chuang et al, 2013; Saijilafu et al, 2008). A better understanding of the multi-scale link between macroscopic loading and loss of function in peripheral nerve is required for effective prevention and treatment of neuropathies, and to explore tension as a strategy for injury prevention and regeneration (Bueno and Shah, 2008)

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