title: Estimating axonal strain and failure following white matter stretch using contactin-associated protein as a fiduciary marker.
abstract: Axonal injury occurs during trauma when tissue-scale loads are transferred to individual axons. Computational models are used to understand this transfer and predict the circumstances that cause injury. However, these findings are limited by a lack of validating experimental work examining the mechanics of axons in their in situ state. As a first step towards validation for dynamic stretch, we use contactin-associated protein (Caspr), expressed at the nodes of Ranvier, as a fiduciary marker of quasistatic axonal stretch. We measured changes in the distance between immunolabled Caspr pairs along axons as a function of tissue-level stretch in chick embryo spinal cords harvested from different developmental periods. We then identified and characterized broken axons and adapted a kinematic model published previously by our group (Singh et al., 2015) to estimate average strain thresholds for axon mechanical failure. The distance between Caspr pairs increased with stretch, though not as much as predicted by simple continuum mechanics. For equivalent tissue stretch, greater numbers of broken axons were found at later stages of development. In adapting our kinematic model to predict a breaking threshold strain, we found that breaking thresholds decrease with development stage. When thresholds were split and classified based on kinematic behavior, non-affine, uncoupled axons had higher strain thresholds than affine, coupled axons, corroborating thresholds predicted from in vitro and in vivo preparations. These results provide a valuable launching point for generating more accurate multi-scale models in primary central nervous system injury.
authors.affiliation: Department of Biomedical Engineering, Rutgers, The State University of New Jersey, 599 Taylor Road, Piscataway, NJ, 08854, United States.
authors.forename: Sagar
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Mechanical and Aerospace Engineering, Rutgers, The State University of New Jersey, 98 Brett Road, Piscataway, NJ, 08854, United States.
authors.forename: Assimina A
authors.initials: AA
authors.lastname: Pelegri
authors.affiliation: Department of Biomedical Engineering, Rutgers, The State University of New Jersey, 599 Taylor Road, Piscataway, NJ, 08854, United States. Electronic address: shreiber@rci.rutgers.edu.
authors.forename: David I
authors.initials: DI
authors.lastname: Shreiber
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D001696:Biomechanical Phenomena; D015816:Cell Adhesion Molecules, Neuronal / Q000502:physiology*; D002642:Chick Embryo; D057918:Fiducial Markers; D008954:Models, Biological; D013116:Spinal Cord / Q000502:physiology*; D013314:Stress, Mechanical
chemical_list: D015816:Cell Adhesion Molecules, Neuronal
keywords: Axon; Injury; Kinematics; Multi-scale; Spinal cord injury; Strain; Traumatic brain injury