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Acta Biomater. 2019 Aug 23. pii: S1742-7061(19)30592-6. doi: 10.1016/j.actbio.2019.08.036. [Epub ahead of print]

Brain maturation is associated with increasing tissue stiffness and decreasing tissue fluidity.

Author information

1
Department of Radiology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany. Electronic address: jing.guo@charite.de.
2
Department of Radiology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany.
3
Mass Spectrometry Facility, Max Planck Institute for Molecular Genetics, Berlin, Germany.
4
Department of Neurology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany.
5
Institute for Medical Immunology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
6
Institute for Medical Immunology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany.
7
Department of Experimental Neurology and Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; NeuroCure Cluster of Excellence and Charité Core Facility 7T Experimental MRIs, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany.
8
Institute of Medical Informatics, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany.
9
Department of Radiology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany. Electronic address: ingolf.sack@charite.de.

Abstract

Biomechanical cues guide proliferation, growth and maturation of neurons. Yet the molecules that shape the brain's biomechanical properties are unidentified and the relationship between neural development and viscoelasticity of brain tissue remains elusive. Here we combined novel in-vivo tomoelastography and ex-vivo proteomics to investigate whether viscoelasticity of the mouse brain correlates with protein alterations within the critical phase of brain maturation. For the first time, high-resolution atlases of viscoelasticity of the mouse brain were generated, revealing that (i) brain stiffness increased alongside progressive accumulation of microtubular structures, myelination, cytoskeleton linkage and cell-matrix attachment, and that (ii) viscosity-related tissue fluidity decreased alongside downregulated actin crosslinking and axonal organization. Taken together, our results show that brain maturation is associated with a shift of brain mechanical properties towards a more solid-rigid behavior consistent with reduced tissue fluidity. This shift appears to be driven by several molecular processes associated with myelination, cytoskeletal crosslinking and axonal organization. STATEMENT OF SIGNIFICANCE: The viscoelastic properties of brain tissue shape the environment in which neurons proliferate, grow, and mature. In the present study, novel tomoelastography was used to spatially map tissue mechanical properties of the in-vivo mouse brain during maturation. In vivo tomoelastography was also combined with ex vivo mass spectrometry proteomic analysis to identify the molecules which shape the biomechanical properties of brain tissue. With the combined technique, we observed that brain maturation is associated with a shift of brain mechanical properties towards a more solid-rigid behavior consistent with reduced tissue fluidity which is driven by multiple molecular processes. We believe that this shift of brain mechanical properties discovered in our study reflects a fundamental biophysical signature of brain maturation.

KEYWORDS:

Brain tissue; MR elastography; Maturation; Proteomics analysis; Viscoelasticity

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