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PLoS Comput Biol. 2017 Feb 27;13(2):e1005407. doi: 10.1371/journal.pcbi.1005407. eCollection 2017 Feb.

Modeling of the axon membrane skeleton structure and implications for its mechanical properties.

Author information

1
Department of Mechanical Engineering, University of Connecticut, Storrs, Connecticut, United States of America.
2
Department of Biomedical Engineering, University of Connecticut, Storrs, Connecticut, United States of America.
3
Division of Applied Mathematics, Brown University, Providence, Rhode Island, United States of America.
4
Department of Mathematics, University of Connecticut, Storrs, Connecticut, United States of America.
5
Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut, United States of America.

Abstract

Super-resolution microscopy recently revealed that, unlike the soma and dendrites, the axon membrane skeleton is structured as a series of actin rings connected by spectrin filaments that are held under tension. Currently, the structure-function relationship of the axonal structure is unclear. Here, we used atomic force microscopy (AFM) to show that the stiffness of the axon plasma membrane is significantly higher than the stiffnesses of dendrites and somata. To examine whether the structure of the axon plasma membrane determines its overall stiffness, we introduced a coarse-grain molecular dynamics model of the axon membrane skeleton that reproduces the structure identified by super-resolution microscopy. Our proposed computational model accurately simulates the median value of the Young's modulus of the axon plasma membrane determined by atomic force microscopy. It also predicts that because the spectrin filaments are under entropic tension, the thermal random motion of the voltage-gated sodium channels (Nav), which are bound to ankyrin particles, a critical axonal protein, is reduced compared to the thermal motion when spectrin filaments are held at equilibrium. Lastly, our model predicts that because spectrin filaments are under tension, any axonal injuries that lacerate spectrin filaments will likely lead to a permanent disruption of the membrane skeleton due to the inability of spectrin filaments to spontaneously form their initial under-tension configuration.

PMID:
28241082
PMCID:
PMC5348042
DOI:
10.1371/journal.pcbi.1005407
[Indexed for MEDLINE]
Free PMC Article

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