title: Modeling of the axon membrane skeleton structure and implications for its mechanical properties.
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.
authors.affiliation: Department of Mechanical Engineering, University of Connecticut, Storrs, Connecticut, United States of America.
authors.forename: Yihao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, University of Connecticut, Storrs, Connecticut, United States of America.
authors.forename: Krithika
authors.initials: K
authors.lastname: Abiraman
authors.affiliation: Division of Applied Mathematics, Brown University, Providence, Rhode Island, United States of America.
authors.forename: He
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Mechanical Engineering, University of Connecticut, Storrs, Connecticut, United States of America.|Department of Biomedical Engineering, University of Connecticut, Storrs, Connecticut, United States of America.|Department of Mathematics, University of Connecticut, Storrs, Connecticut, United States of America.
authors.forename: David M
authors.identifier: 0000-0002-9713-1204
authors.initials: DM
authors.lastname: Pierce
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut, United States of America.
authors.forename: Anastasios V
authors.initials: AV
authors.lastname: Tzingounis
authors.affiliation: Department of Mechanical Engineering, University of Connecticut, Storrs, Connecticut, United States of America.|Department of Biomedical Engineering, University of Connecticut, Storrs, Connecticut, United States of America.
authors.forename: George
authors.identifier: 0000-0003-2088-5478
authors.initials: G
authors.lastname: Lykotrafitis
mesh_terms: D000199:Actins / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D000818:Animals; D001369:Axons / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D002462:Cell Membrane / Q000737:chemistry* / Q000502:physiology* / Q000648:ultrastructure; D002478:Cells, Cultured; D003198:Computer Simulation; D055119:Elastic Modulus / Q000502:physiology; D020342:Finite Element Analysis; D018625:Microscopy, Atomic Force; D008954:Models, Biological; D008956:Models, Chemical; D051381:Rats; D013049:Spectrin / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D013314:Stress, Mechanical; D013718:Tensile Strength / Q000502:physiology
chemical_list: D000199:Actins; D013049:Spectrin