Understanding the mechanics of brain embryogenesis can provide insights on pathologies related to brain development, such as lissencephaly, a genetic disease which causes a reduction of the number of cerebral sulci. Recent experiments on brain organoids have confirmed that gyrification, i.e. the formation of the folded structures of the brain, is triggered by the inhomogeneous growth of the peripheral region. However, the rheology of these cellular aggregates and the mechanics of lissencephaly are still matter of debate. In this work, we develop a mathematical model of brain organoids based on the theory of morpho-elasticity. We describe them as non-linear elastic bodies, composed of a disk surrounded by a growing layer called cortex. The external boundary is subjected to a tissue surface tension due the intercellular adhesion forces. We show that the resulting surface energy is relevant at the small length scales of brain organoids and affects the mechanics of cellular aggregates. We perform a linear stability analysis of the radially symmetric configuration and we study the post-buckling behaviour through finite element simulations. We find that the process of gyrification is triggered by the cortex growth and modulated by the competition between two length scales: the radius of the organoid and the capillary length generated by surface tension. We show that a solid model can reproduce the results of the in-vitro experiments. Furthermore, we prove that the lack of brain sulci in lissencephaly is caused by a reduction of the cell stiffness: the softening of the organoid strengthens the role of surface tension, delaying or even inhibiting the onset of a mechanical instability at the free boundary.

10aBuckling10aEmbryogenesis10aMorpho-elasticity10aPost-buckling analysis10aSurface tension1 aRiccobelli, Davide1 aBevilacqua, Giulia uhttp://www.sciencedirect.com/science/article/pii/S002250961930406500543nas a2200133 4500008004100000245007700041210006900118260004700187300001600234490000700250100002300257700002400280856010500304 2018 eng d00aShape transitions in a soft incompressible sphere with residual stresses0 aShape transitions in a soft incompressible sphere with residual bSAGE Publications Sage UK: London, England a1507–15240 v231 aRiccobelli, Davide1 aCiarletta, Pasquale uhttps://www.math.sissa.it/publication/shape-transitions-soft-incompressible-sphere-residual-stresses00623nas a2200169 4500008004100000245008300041210006900124260002500193300001400218490000800232100001600240700001600256700002300272700002300295700002400318856011100342 2017 eng d00aSolid tumors are poroelastic solids with a chemo-mechanical feedback on growth0 aSolid tumors are poroelastic solids with a chemomechanical feedb bSpringer Netherlands a107–1240 v1291 aAmbrosi, D.1 aPezzuto, S.1 aRiccobelli, Davide1 aStylianopoulos, T.1 aCiarletta, Pasquale uhttps://www.math.sissa.it/publication/solid-tumors-are-poroelastic-solids-chemo-mechanical-feedback-growth