Affiliation:
1. Department of Mechanical Engineering University of Washington Seattle Washington USA
2. Department of Mechanical Engineering Stevens Institute of Technology Hoboken New Jersey USA
3. Department of Biological Science Hunter College New York New York USA
4. Department of Biostatistics Boston University Boston Massachusetts USA
5. BioMedical Engineering and Imaging Institute Icahn School of Medicine at Mount Sinai New York New York USA
Abstract
AbstractDuring development, dramatic changes in myelination, growth of neural networks and changes in grey‐to‐white matter ratio build up the astonishingly plastic brain of a child. The progressive increase in myelination insulates the nervous system, which, in turn, modifies the mechanical microenvironment of the brain spatiotemporally. A growing body of evidence demonstrates the role of mechanical forces in growth, differentiation, maturation and electrical properties of neurons. However, due to limitations in imaging resolution, the exact relationship between myelination, axonal organization and the mechanical properties of nerves at the cellular level is still unknown. Here, we propose a novel approach to study the direct relationship between axonal viscoelasticity with changing fibre anisotropy and myelination during development. With the use of atomic force microscopy (AFM) with in situ fluorescent imaging of the primary neuron‐oligodendrocyte co‐cultures, we found that as axons are progressively myelinated in vitro, their stiffness increases. Direct quantification of myelin along axons using immunofluorescence also demonstrated a positive correlation between increased myelination over time and increased axonal stiffness (p = .001). Notably, AFM measurements along a single axon showed that the Young's modulus measured across myelinated regions were significantly higher than those of adjacent unmyelinated segments at all time points (p < .0001). Force‐relaxation analysis also demonstrated that myelin sheath dominates the regulation of viscoelasticity of axons temporally. Collectively, our findings indicate a direct link between myelination, axonal orientation and viscoelasticity, providing important insights about the mechanical environment in the paediatric brain, with direct implications for our understanding of developmental brain disorders and paediatric brain injury.
Funder
U.S. Department of Defense
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献