title: Opposite rheological properties of neuronal microcompartments predict axonal vulnerability in brain injury.
abstract: Although pathological changes in axonal morphology have emerged as important features of traumatic brain injury (TBI), the mechanical vulnerability of the axonal microcompartment relative to the cell body is not well understood. We hypothesized that soma and neurite microcompartments exhibit distinct mechanical behaviors, rendering axons more sensitive to a mechanical injury. In order to test this assumption, we combined protein micropatterns with magnetic tweezer rheology to probe the viscoelastic properties of neuronal microcompartments. Creep experiments revealed two opposite rheological behaviors within cortical neurons: the cell body was soft and characterized by a solid-like response, whereas the neurite compartment was stiffer and viscous-like. By using pharmacological agents, we demonstrated that the nucleus is responsible for the solid-like behavior and the stress-stiffening response of the soma, whereas neurofilaments have a predominant contribution in the viscous behavior of the neurite. Furthermore, we found that the neurite is a mechanosensitive compartment that becomes softer and adopts a pronounced viscous state on soft matrices. Together, these findings highlight the importance of the regionalization of mechanical and rigidity-sensing properties within neuron microcompartments in the preferential damage of axons during traumatic brain injury and into potential mechanisms of axonal outgrowth after injury.
authors.affiliation: Mechanobiology &Soft Matter Group, Interfaces and Complex Fluids Laboratory, Research Institute for Biosciences, CIRMAP, University of Mons, 20 Place du Parc B-7000 Mons, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Grevesse
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard University, 29 Oxford Street, Cambridge, MA 02138, USA.
authors.forename: Borna E
authors.initials: BE
authors.lastname: Dabiri
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard University, 29 Oxford Street, Cambridge, MA 02138, USA.
authors.forename: Kevin Kit
authors.initials: KK
authors.lastname: Parker
authors.affiliation: Mechanobiology &Soft Matter Group, Interfaces and Complex Fluids Laboratory, Research Institute for Biosciences, CIRMAP, University of Mons, 20 Place du Parc B-7000 Mons, Belgium.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Gabriele
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology*; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology; D016501:Neurites / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D012212:Rheology
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