Generation of contractile forces by three-dimensional bundled axonal tracts in micro-tissue engineered neural networks.

Autor:	Chouhan D; Department of Neurosurgery, Center for Brain Injury and Repair, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.; Center for Neurotrauma, Neurodegeneration and Restoration, Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, United States., Gordián Vélez WJ; Department of Neurosurgery, Center for Brain Injury and Repair, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.; Center for Neurotrauma, Neurodegeneration and Restoration, Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, United States.; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, United States., Struzyna LA; Department of Neurosurgery, Center for Brain Injury and Repair, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.; Center for Neurotrauma, Neurodegeneration and Restoration, Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, United States.; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, United States., Adewole DO; Department of Neurosurgery, Center for Brain Injury and Repair, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.; Center for Neurotrauma, Neurodegeneration and Restoration, Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, United States.; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, United States., Cullen ER; Department of Neurosurgery, Center for Brain Injury and Repair, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.; Center for Neurotrauma, Neurodegeneration and Restoration, Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, United States., Burrell JC; Department of Neurosurgery, Center for Brain Injury and Repair, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.; Center for Neurotrauma, Neurodegeneration and Restoration, Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, United States., O'Donnell JC; Department of Neurosurgery, Center for Brain Injury and Repair, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.; Center for Neurotrauma, Neurodegeneration and Restoration, Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, United States., Cullen DK; Department of Neurosurgery, Center for Brain Injury and Repair, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.; Center for Neurotrauma, Neurodegeneration and Restoration, Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, United States.; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in molecular neuroscience [Front Mol Neurosci] 2024 Mar 25; Vol. 17, pp. 1346696. Date of Electronic Publication: 2024 Mar 25 (Print Publication: 2024).
DOI:	10.3389/fnmol.2024.1346696
Abstrakt:	Axonal extension and retraction are ongoing processes that occur throughout all developmental stages of an organism. The ability of axons to produce mechanical forces internally and respond to externally generated forces is crucial for nervous system development, maintenance, and plasticity. Such axonal mechanobiological phenomena have typically been evaluated in vitro at a single-cell level, but these mechanisms have not been studied when axons are present in a bundled three-dimensional (3D) form like in native tissue. In an attempt to emulate native cortico-cortical interactions under in vitro conditions, we present our approach to utilize previously described micro-tissue engineered neural networks (micro-TENNs). Here, micro-TENNs were comprised of discrete populations of rat cortical neurons that were spanned by 3D bundled axonal tracts and physically integrated with each other. We found that these bundled axonal tracts inherently exhibited an ability to generate contractile forces as the microtissue matured. We therefore utilized this micro-TENN testbed to characterize the intrinsic contractile forces generated by the integrated axonal tracts in the absence of any external force. We found that contractile forces generated by bundled axons were dependent on microtubule stability. Moreover, these intra-axonal contractile forces could simultaneously generate tensile forces to induce so-called axonal "stretch-growth" in different axonal tracts within the same microtissue. The culmination of axonal contraction generally occurred with the fusion of both the neuronal somatic regions along the axonal tracts, therefore perhaps showing the innate tendency of cortical neurons to minimize their wiring distance, a phenomenon also perceived during brain morphogenesis. In future applications, this testbed may be used to investigate mechanisms of neuroanatomical development and those underlying certain neurodevelopmental disorders. Competing Interests: Multiple patents relate to the composition, methods, and use of the constructs described in the paper, including U.S. Patent App. 15/032,677 (DKC), U.S. Patent App. 16/093,036 (DKC), U.S. Patent App. 17/291,869 (DKC, WGV). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Chouhan, Gordián Vélez, Struzyna, Adewole, Cullen, Burrell, O’Donnell and Cullen.)
Databáze:	MEDLINE
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