Mechanics of human brain organoids

Abstract

Organoids are prototypes of human organs derived from cultured human stem cells. They provide a reliable and accurate experimental model to study the physical mechanisms underlying the early developmental stages of human organs morphogenesis and, in particular, the early morphogenesis of the cortex. Here, we propose a mathematical model to elucidate the role played by two mechanisms which have been experimentally proven to be crucial in shaping human brain organoids: the contraction of the inner core of the organoid and the microstructural remodeling of the outer cortex. Our results show that both mechanisms are crucial for the final shape of the organoid and can explain the origin of brain pathologies such as lissencephaly (smooth brain). arXiv:1811.01893v1 [cond-mat.soft]

Surface tension controls the onset of gyrification in brain organoids

“…Compared to the model proposed by Balbi et al [2018], in which the authors do not take into account the tissue surface tension, our theoretical description presents some advantages. In fact, we do not introduce different shear moduli for the cortex and the lumen to modulate the critical wavenumber and the critical growth threshold.…”

“…To construct a bifurcation criterion, we follow Balbi et al [2018]. From the continuity of the displacement-traction vector η C (r i ) = η L (r i ) (27) we get…”

“…A first model of the experiments on brain organoids [Karzbrun et al, 2018] has been developed by Balbi et al [2018]. The authors model the organoid as a non-linear elastic material, where gyrification is triggered by a remodelling of the cortex and the contraction of the lumen.…”

“…In this paper, we revisit the model proposed by Balbi et al [2018] to overcome the limitations remarked by Engstrom et al [2018], proposing a different explanation of lissencephaly. In cellular aggregates, cohesion among cells is due to adhesion forces induced by adhesion molecules .…”

Spheroid mechanics and implications for cell invasion

“…Mechanical forces are integral to spheroid development and self-organization by regulating and changing their overall shape, cell packing density and internal cell arrangement. For instance, the interplay between various physical parameters (such as cell-cell adhesion, cortical tension evoked by the cell's actomyosin cortex, and elasticity) strongly regulates cell sorting in embryos as shown in both 3D aggregates [19,20] and organoids [21][22][23][24]. Spheroids therefore allow us to probe a wide range of key biophysical parameters that influence tissue formation, tumour growth and cell invasion under relevant physical forces (such as shear stress) and gradients of biochemical cues (such as transforming growth factors and nutrients).…”