ZiMT Journal Club May 2019: Dr.-Ing. Silvia Budday / The role of mechanics during brain development

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Dr.-Ing. Silvia Budday, Chair of Applied Mechanics (LTM), FAU

The role of mechanics during brain development

The characteristically folded surface morphology is a classical hallmark of the mammalian brain. During development, the initially smooth surface evolves into an elaborately convoluted pattern, which closely correlates with brain function and serves as a clinical indicator for physiological and pathological conditions. Despite their significance, the regulators of brain folding in evolution and development remain poorly understood. Here, we combine analytical, computational, and experimental analyses to show that physical forces play an important role in pattern selection. We experimentally characterize the mechanical response of brain tissue under multiple loading conditions and closely consider cellular processes during brain development to establish a mechanical model of brain growth. The model consists of a morphogenetically growing outer cortex and a stretch-induced growing inner core. Through computational analyses we explore growth-induced primary and secondary instabilities and provide new evidence towards the emergence of advanced, higher order wrinkling modes. Our results emphasize that the key regulators of brain folding include cortical thickness, brain geometry, stiffness, and growth. The mechanical model explains why larger mammalian brains tend to be more convoluted than smaller brains. Numerical predictions agree well with the classical pathologies of lissencephaly and polymicrogyria. Combining physics and biology holds promise to further advance our understanding of human brain development, to enable early diagnostics of cortical malformations, and to improve treatment of neurodevelopmental disorders such as epilepsy, autism, and schizophrenia.

Biography

Silvia Budday, currently an Emmy Noether junior research group leader at the LTM, studied Mechanical Engineering at the Karlsruhe Institute of Technology (KIT), where she graduated with one of the four best Bachelor’s degrees in 2011 and the best Master’s degree of a female student in 2013. During her Master’s studies, she spent one year abroad at Purdue University, Indiana, USA, for which she received an international scholarship by the DAAD (German Academic Exchange Service). She was also a scholar of the German Academic Scholarship Foundation. She did her PhD on “The Role of Mechanics during Brain Development” at FAU supervised Prof. Paul Steinmann in close collaboration with Prof. Ellen Kuhl at Stanford University and Prof. Gerhard Holzapfel at Graz University of Technology. She finished her PhD in December 2017 with “summa cum laude” and was awarded the GACM Best PhD Award (German Association for Computational Mechanics) and the ECCOMAS Best PhD Award for one of the two best PhD theses in the field of Computational Methods in Applied Sciences and Engineering in Europe in 2017. Furthermore, she received the Bertha Benz-Prize from the Daimler und Benz Stiftung as a woman visionary pioneer in engineering. In July 2018, she received the Emerging Talents Initiative funding by the FAU, and in October 2018 one of the 2017 Acta Students Awards. Her work focuses on experimental and computational soft tissue biomechanics with special emphasis on brain mechanics and the relationship between brain structure and function.

References

M. Holland, S. Budday, A. Goriely, and E. Kuhl. Symmetry Breaking in Wrinkling Patterns: Gyri Are Universally Thicker than Sulci. Phys. Rev. Lett., 121:228002, 2018.

S. Budday and P. Steinmann. On the influence of inhomogeneous stiffness and growth on mechanical instabilities in the developing brain. Int. J. Solids Struct., 132–133:31–41, 2018.

S. Budday, S. Andres, B. Walter, P. Steinmann, and E. Kuhl. Wrinkling instabilities in soft bilayered systems. Philos. Trans. A Math. Phys. Eng. Sci., 375(2093), 2017.

S. Budday, G. Sommer, C. Birkl, C. Langkammer, J. Haybaeck, J. Kohnert, M. Bauer, F. Paulsen, P. Steinmann, E. Kuhl, and G. A. Holzapfel. Mechanical characterization of human brain tissue. Acta Biomater., 48:319–340, 2017.

S. Budday, R. Nay, R. de Rooij, P. Steinmann, T. Wyrobek, T. C. Ovaert, and E. Kuhl. Mechanical properties of gray and white matter brain tissue by indentation. J. Mech. Behav. Biomed. Mater., 46:318–330, 2015.

S. Budday, P. Steinmann, and E. Kuhl. Physical biology of human brain development. Front. Cell. Neurosci., 9, 2015.

S. Budday, E. Kuhl, and J. W. Hutchinson. Period-doubling and period-tripling in growing bilayered systems. Philos. Mag., (95):3208–3224, 2015.

S. Budday, P. Steinmann, and E. Kuhl. Secondary instabilities modulate cortical complexity in the mammalian brain. Philos. Mag., 95(28-30):3244–3256, 2015.

S. Budday, P. Steinmann, A. Goriely, and E. Kuhl. Size and curvature regulate pattern selection in the mammalian brain. Extreme Mech. Lett., 4:193–198, 2015.

S. Budday, P. Steinmann, and E. Kuhl. The role of mechanics during brain development. J. Mech. Phys. Solids, 72:75–92, 2014.

S. Budday, C. Raybaud, and E. Kuhl. A mechanical model predicts morphological abnormalities in the developing human brain. Sci. Rep., 4, 2014.