Unravelling crucial biomechanical resilience of myelinated peripheral nerve fibres provided by the Schwann cell basal lamina and PMP22

Abstract

There is an urgent need for the research of the close and enigmatic relationship between nerve biomechanics and the development of neuropathies. Here we present a research strategy based on the application atomic force and confocal microscopy for simultaneous nerve biomechanics and integrity investigations. Using wild-type and hereditary neuropathy mouse models, we reveal surprising mechanical protection of peripheral nerves. Myelinated peripheral wild-type fibres promptly and fully recover from acute enormous local mechanical compression while maintaining functional and structural integrity. The basal lamina which enwraps each myelinated fibre separately is identified as the major contributor to the striking fibre's resilience and integrity. In contrast, neuropathic fibres lacking the peripheral myelin protein 22 (PMP22), which is closely connected with several hereditary human neuropathies, fail to recover from light compression. Interestingly, the structural arrangement of the basal lamina of Pmp22−/− fibres is significantly altered compared to wild-type fibres. In conclusion, the basal lamina and PMP22 act in concert to contribute to a resilience and integrity of peripheral nerves at the single fibre level. Our findings and the presented technology set the stage for a comprehensive research of the links between nerve biomechanics and neuropathies.

Mechanosensitivity of Embryonic Neurites Promotes Their Directional Extension and Schwann Cells Progenitors Migration

“…We have recently shown that the average elastic Yong’s modulus of mature myelinated nerve fibers from mice is ∼ 20 kPa [13]. Here, embryonic DRG explants were exposed to substrates with elastic moduli of 1 kPa, 10 kPa and 20 kPa, referred to as soft, medium and hard, respectively.…”

Mechanical Response of Neural Cells to Physiologically Relevant Stiffness Gradients

“…We fabricated collagen substrates with stiffnesses of physiological relevance to the PNS by varying the collagen concentration using bespoke 3D‐printed moulds and the RAFT‐stabilization process. Two different collagen gradients (Lower and Higher) were created and compared to control plain RAFT‐stabilized gels with no gradient (Control).…”

“…Improved peripheral nerve repair strategies need to be developed and one of the emerging research avenues in tissue engineering is the study of cell–substrate interactions, which underpin conduits that support and guide neuronal regeneration. Recent studies have shown the importance of the mechanical environment within the peripheral nervous system during development and in pathological situations …”

Biomimetic Microelectronics for Regenerative Neuronal Cuff Implants

“…The elastic modulus of each polymeric layer with the thicknesses as in the functional stack was determined by measuring the force-distance curve with an atomic force microscope (AFM) tip indenting the layer (Figure 1 f), accordingly to the routine proposed by Rosso et al [ 33 ] The data was fi tted to the Hertzian model [ 34 ] (see the Experimental Section for details) and the Young's modulus was determined by analyzing the slope of the linear part of the force-distance curve. We achieve a Young's modulus of the materials of 16.8 MPa for the capping polychloroprene layer, 4.5 MPa for the hydrogel layer, and 3.2 GPa for the stiff polyimide layer.…”