Tissue loading and microstructure regulate the deformation of embedded nerve fibres: predictions from single-scale and multiscale simulations.

Excessive deformation of nerve fibres (axons) in the spinal facet capsular ligaments (FCLs) can be a cause of pain. The axons are embedded in the fibrous extracellular matrix (ECM) of FCLs, so understanding how local fibre organization and micromechanics modulate their mechanical behaviour is essential. We constructed a computational discrete-fibre model of an axon embedded in a collagen fibre network attached to the axon by distinct fibre-axon connections. This model was used to relate the axonal deformation to the fibre alignment and collagen volume concentration of the surrounding network during transverse, axial and shear deformations. Our results showed that fibre alignment affects axonal deformation only during transverse and axial loading, but higher collagen volume concentration results in larger overall axonal strains for all loading cases. Furthermore, axial loading leads to the largest stretch of axonal microtubules and induces the largest forces on axon's surface in most cases. Comparison between this model and a multiscale continuum model for a representative case showed that although both models predicted similar averaged axonal strains, strain was more heterogeneous in the discrete-fibre model.