Causes of autism spectrum disorders (ASD) are understood poorly, making diagnosis and treatment challenging. While many studies have investigated the biochemical and genetic aspects of ASD, whether and how mechanical characteristics of the autistic brain can modulate neuronal connectivity and cognition in ASD are unknown. Previously, it has been shown that ASD brains are characterized by abnormal white matter and disorganized neuronal connectivity; we hypothesized that these significant cellular-level structural changes may translate to changes in the mechanical properties of the autistic brain or regions therein. Here, we focused on tuberous sclerosis complex (TSC), a genetic disorder with a high penetrance of ASD. We investigated mechanical differences between murine brains obtained from control and TSC cohorts at various deformation length- and time-scales. At the microscale, we conducted creep-compliance and stress relaxation experiments using atomic force microscope(AFM)-enabled indentation. At the mesoscale, we conducted impact indentation using a pendulum-based instrumented indenter to extract mechanical energy dissipation metrics. At the macroscale, we used oscillatory shear rheology to quantify the frequency-dependent shear moduli. Despite significant changes in the cellular organization of TSC brain tissue, we found no corresponding changes in the quantified mechanical properties at every length- and time-scale explored. This investigation of the mechanical characteristics of the brain has broadened our understanding of causes and markers of TSC/ASD, while raising questions about whether any mechanical differences can be detected in other animal models of ASD or other disease models that also feature abnormal brain structure.
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March 2019
Research-Article
Probing Mechanical Properties of Brain in a Tuberous Sclerosis Model of Autism
Bo Qing,
Bo Qing
Department of Biological Engineering,
MIT,
Cambridge, MA 02139
MIT,
Cambridge, MA 02139
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Elizabeth P. Canovic,
Elizabeth P. Canovic
Department of Materials Science
and Engineering,
MIT,
Cambridge, MA 02139
and Engineering,
MIT,
Cambridge, MA 02139
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Aleksandar S. Mijailovic,
Aleksandar S. Mijailovic
Department of Mechanical Engineering,
MIT,
Cambridge, MA 02139
MIT,
Cambridge, MA 02139
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Anna Jagielska,
Anna Jagielska
Department of Materials Science
and Engineering,
MIT,
Cambridge, MA 02139
and Engineering,
MIT,
Cambridge, MA 02139
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Matthew J. Whitfield,
Matthew J. Whitfield
Department of Materials Science
and Engineering,
MIT,
Cambridge, MA 02139
and Engineering,
MIT,
Cambridge, MA 02139
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Alexis L. Lowe,
Alexis L. Lowe
Department of Neuroscience,
Wellesley College,
Wellesley, MA 02481
Wellesley College,
Wellesley, MA 02481
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Elyza H. Kelly,
Elyza H. Kelly
Department of Neurology,
The F.M. Kirby Neurobiology Center,
Harvard Medical School,
Boston Children's Hospital,
Boston, MA 02115
The F.M. Kirby Neurobiology Center,
Harvard Medical School,
Boston Children's Hospital,
Boston, MA 02115
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Daria Turner,
Daria Turner
Department of Neurology,
The F.M. Kirby Neurobiology Center,
Harvard Medical School,
Boston Children's Hospital,
Boston, MA 02115
The F.M. Kirby Neurobiology Center,
Harvard Medical School,
Boston Children's Hospital,
Boston, MA 02115
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Mustafa Sahin,
Mustafa Sahin
Department of Neurology,
The F.M. Kirby Neurobiology Center,
Harvard Medical School,
Boston Children's Hospital,
Boston, MA 02115
The F.M. Kirby Neurobiology Center,
Harvard Medical School,
Boston Children's Hospital,
Boston, MA 02115
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Krystyn J. Van Vliet
Krystyn J. Van Vliet
Department of Biological Engineering,
MIT,
Cambridge, MA 02139;
Department of Materials Science
and Engineering,
MIT,
Cambridge, MA 02139
e-mail: krystyn@mit.edu
MIT,
Cambridge, MA 02139;
Department of Materials Science
and Engineering,
MIT,
Cambridge, MA 02139
e-mail: krystyn@mit.edu
Search for other works by this author on:
Bo Qing
Department of Biological Engineering,
MIT,
Cambridge, MA 02139
MIT,
Cambridge, MA 02139
Elizabeth P. Canovic
Department of Materials Science
and Engineering,
MIT,
Cambridge, MA 02139
and Engineering,
MIT,
Cambridge, MA 02139
Aleksandar S. Mijailovic
Department of Mechanical Engineering,
MIT,
Cambridge, MA 02139
MIT,
Cambridge, MA 02139
Anna Jagielska
Department of Materials Science
and Engineering,
MIT,
Cambridge, MA 02139
and Engineering,
MIT,
Cambridge, MA 02139
Matthew J. Whitfield
Department of Materials Science
and Engineering,
MIT,
Cambridge, MA 02139
and Engineering,
MIT,
Cambridge, MA 02139
Alexis L. Lowe
Department of Neuroscience,
Wellesley College,
Wellesley, MA 02481
Wellesley College,
Wellesley, MA 02481
Elyza H. Kelly
Department of Neurology,
The F.M. Kirby Neurobiology Center,
Harvard Medical School,
Boston Children's Hospital,
Boston, MA 02115
The F.M. Kirby Neurobiology Center,
Harvard Medical School,
Boston Children's Hospital,
Boston, MA 02115
Daria Turner
Department of Neurology,
The F.M. Kirby Neurobiology Center,
Harvard Medical School,
Boston Children's Hospital,
Boston, MA 02115
The F.M. Kirby Neurobiology Center,
Harvard Medical School,
Boston Children's Hospital,
Boston, MA 02115
Mustafa Sahin
Department of Neurology,
The F.M. Kirby Neurobiology Center,
Harvard Medical School,
Boston Children's Hospital,
Boston, MA 02115
The F.M. Kirby Neurobiology Center,
Harvard Medical School,
Boston Children's Hospital,
Boston, MA 02115
Krystyn J. Van Vliet
Department of Biological Engineering,
MIT,
Cambridge, MA 02139;
Department of Materials Science
and Engineering,
MIT,
Cambridge, MA 02139
e-mail: krystyn@mit.edu
MIT,
Cambridge, MA 02139;
Department of Materials Science
and Engineering,
MIT,
Cambridge, MA 02139
e-mail: krystyn@mit.edu
1B. Qing, E. P. Canovic, and A. S. Mijailovic authors contributed equally.
2Corresponding author.
Manuscript received November 28, 2017; final manuscript received July 12, 2018; published online January 18, 2019. Assoc. Editor: Barclay Morrison.
J Biomech Eng. Mar 2019, 141(3): 031001 (10 pages)
Published Online: January 18, 2019
Article history
Received:
November 28, 2017
Revised:
July 12, 2018
Citation
Qing, B., Canovic, E. P., Mijailovic, A. S., Jagielska, A., Whitfield, M. J., Lowe, A. L., Kelly, E. H., Turner, D., Sahin, M., and Van Vliet, K. J. (January 18, 2019). "Probing Mechanical Properties of Brain in a Tuberous Sclerosis Model of Autism." ASME. J Biomech Eng. March 2019; 141(3): 031001. https://doi.org/10.1115/1.4040945
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