Elucidating Axonal Injuries Through Molecular Modelling of Myelin Sheaths and Nodes of Ranvier
Around half of the traumatic brain injuries are thought to be axonal damage. Disruption of the cellular membranes, or alternatively cytoskeletal damage has been suggested as possible injury trigger. Here, we have used molecular models to have a better insight on the structural and mechanical propert...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-06-01
|
| Series: | Frontiers in Molecular Biosciences |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2021.669897/full |
| _version_ | 1819106341191417856 |
|---|---|
| author | Marzieh Saeedimasine Annaclaudia Montanino Svein Kleiven Alessandra Villa |
| author_facet | Marzieh Saeedimasine Annaclaudia Montanino Svein Kleiven Alessandra Villa |
| author_sort | Marzieh Saeedimasine |
| collection | DOAJ |
| description | Around half of the traumatic brain injuries are thought to be axonal damage. Disruption of the cellular membranes, or alternatively cytoskeletal damage has been suggested as possible injury trigger. Here, we have used molecular models to have a better insight on the structural and mechanical properties of axon sub-cellular components. We modelled myelin sheath and node of Ranvier as lipid bilayers at a coarse grained level. We built ex-novo a model for the myelin. Lipid composition and lipid saturation were based on the available experimental data. The model contains 17 different types of lipids, distributed asymmetrically between two leaflets. Molecular dynamics simulations were performed to characterize the myelin and node-of-Ranvier bilayers at equilibrium and under deformation and compared to previous axolemma simulations. We found that the myelin bilayer has a slightly higher area compressibility modulus and higher rupture strain than node of Ranvier. Compared to the axolemma in unmyelinated axon, mechanoporation occurs at 50% higher strain in the myelin and at 23% lower strain in the node of Ranvier in myelinated axon. Combining the results with finite element simulations of the axon, we hypothesizes that myelin does not rupture at the thresholds proposed in the literature for axonal injury while rupture may occur at the node of Ranvier. The findings contribute to increases our knowledge of axonal sub-cellular components and help to understand better the mechanism behind axonal brain injury. |
| first_indexed | 2024-12-22T02:36:36Z |
| format | Article |
| id | doaj.art-49690070592248b8a58021a782a5e3dc |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-12-22T02:36:36Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-49690070592248b8a58021a782a5e3dc2022-12-21T18:41:45ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-06-01810.3389/fmolb.2021.669897669897Elucidating Axonal Injuries Through Molecular Modelling of Myelin Sheaths and Nodes of RanvierMarzieh Saeedimasine0Annaclaudia Montanino1Svein Kleiven2Alessandra Villa3Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, SwedenDivision of Neuronic Engineering, KTH-Royal Institute of Technology, Stockholm, SwedenDivision of Neuronic Engineering, KTH-Royal Institute of Technology, Stockholm, SwedenPDC-Center for High Performance Computing, KTH-Royal Institute of Technology, Stockholm, SwedenAround half of the traumatic brain injuries are thought to be axonal damage. Disruption of the cellular membranes, or alternatively cytoskeletal damage has been suggested as possible injury trigger. Here, we have used molecular models to have a better insight on the structural and mechanical properties of axon sub-cellular components. We modelled myelin sheath and node of Ranvier as lipid bilayers at a coarse grained level. We built ex-novo a model for the myelin. Lipid composition and lipid saturation were based on the available experimental data. The model contains 17 different types of lipids, distributed asymmetrically between two leaflets. Molecular dynamics simulations were performed to characterize the myelin and node-of-Ranvier bilayers at equilibrium and under deformation and compared to previous axolemma simulations. We found that the myelin bilayer has a slightly higher area compressibility modulus and higher rupture strain than node of Ranvier. Compared to the axolemma in unmyelinated axon, mechanoporation occurs at 50% higher strain in the myelin and at 23% lower strain in the node of Ranvier in myelinated axon. Combining the results with finite element simulations of the axon, we hypothesizes that myelin does not rupture at the thresholds proposed in the literature for axonal injury while rupture may occur at the node of Ranvier. The findings contribute to increases our knowledge of axonal sub-cellular components and help to understand better the mechanism behind axonal brain injury.https://www.frontiersin.org/articles/10.3389/fmolb.2021.669897/fullcoarse grained modelmolecular dynamics simulations (MD simulations)brain injuryaxonal membranemechanoporation |
| spellingShingle | Marzieh Saeedimasine Annaclaudia Montanino Svein Kleiven Alessandra Villa Elucidating Axonal Injuries Through Molecular Modelling of Myelin Sheaths and Nodes of Ranvier Frontiers in Molecular Biosciences coarse grained model molecular dynamics simulations (MD simulations) brain injury axonal membrane mechanoporation |
| title | Elucidating Axonal Injuries Through Molecular Modelling of Myelin Sheaths and Nodes of Ranvier |
| title_full | Elucidating Axonal Injuries Through Molecular Modelling of Myelin Sheaths and Nodes of Ranvier |
| title_fullStr | Elucidating Axonal Injuries Through Molecular Modelling of Myelin Sheaths and Nodes of Ranvier |
| title_full_unstemmed | Elucidating Axonal Injuries Through Molecular Modelling of Myelin Sheaths and Nodes of Ranvier |
| title_short | Elucidating Axonal Injuries Through Molecular Modelling of Myelin Sheaths and Nodes of Ranvier |
| title_sort | elucidating axonal injuries through molecular modelling of myelin sheaths and nodes of ranvier |
| topic | coarse grained model molecular dynamics simulations (MD simulations) brain injury axonal membrane mechanoporation |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2021.669897/full |
| work_keys_str_mv | AT marziehsaeedimasine elucidatingaxonalinjuriesthroughmolecularmodellingofmyelinsheathsandnodesofranvier AT annaclaudiamontanino elucidatingaxonalinjuriesthroughmolecularmodellingofmyelinsheathsandnodesofranvier AT sveinkleiven elucidatingaxonalinjuriesthroughmolecularmodellingofmyelinsheathsandnodesofranvier AT alessandravilla elucidatingaxonalinjuriesthroughmolecularmodellingofmyelinsheathsandnodesofranvier |