A fluid-to-solid jamming transition underlies vertebrate body axis elongation

Abstract

Just as in clay moulding or glass blowing, physically sculpting biological structures requires the constituent material to locally flow like a fluid while maintaining overall mechanical integrity like a solid. Disordered soft materials, such as foams, emulsions and colloidal suspensions, switch from fluid-like to solid-like behaviours at a jamming transition. Similarly, cell collectives have been shown to display glassy dynamics in 2D and 3D and jamming in cultured epithelial monolayers, behaviours recently predicted theoretically and proposed to influence asthma pathobiology and tumour progression. However, little is known about whether these seemingly universal behaviours occur in vivo and, specifically, whether they play any functional part during embryonic morphogenesis. Here, by combining direct in vivo measurements of tissue mechanics with analysis of cellular dynamics, we show that during vertebrate body axis elongation, posterior tissues undergo a jamming transition from a fluid-like behaviour at the extending end, the mesodermal progenitor zone, to a solid-like behaviour in the presomitic mesoderm. We uncover an anteroposterior, N-cadherin-dependent gradient in yield stress that provides increasing mechanical integrity to the presomitic mesoderm, consistent with the tissue transiting from a wetter to a dryer foam-like architecture. Our results show that cell-scale stresses fluctuate rapidly (within about 1 min), enabling cell rearrangements and effectively 'melting' the tissue at the growing end. Persistent (more than 0.5 h) stresses at supracellular scales, rather than cell-scale stresses, guide morphogenetic flows in fluid-like tissue regions. Unidirectional axis extension is sustained by the reported rigidification of the presomitic mesoderm, which mechanically supports posterior, fluid-like tissues during remodelling before their maturation. The spatiotemporal control of fluid-like and solid-like tissue states may represent a generic physical mechanism of embryonic morphogenesis.

Tissue rheology in embryonic organization

“…For instance, there is experimental evidence linking cell packing/density to embryonic tissue rigidity. In zebrafish, these observations were further confirmed by the use of ferromagnetic oil droplets (FDs) to directly measure tissue viscosity within the PSM (Box 1; Fig 2F), pointing at the possibility that the mesoderm transits from a fluid into a more solid-like state during maturation along its anterior-posterior axis (Serwane et al, 2017;Mongera et al, 2018). There is also increasing evidence linking cell motion/rearrangements to tissue viscosity.…”

“…Brillouin Microscopy (BM): BM probes the viscoelastic properties of a material via light scattering. Imaging the deformation of the droplet shape during the application and removal of the magnetic force, the local tissue mechanical properties (viscosity, elasticity and yield stress) in a small neighbourhood surrounding the FD can be quantified, as demonstrated in the somitic mesoderm of zebrafish embryos (Serwane et al, 2017;Mongera et al, 2018). This generates a Brillouin spectrum where the scattered light displays a frequency shift compared to the illumination light, from which the longitudinal modulus can be measured if the refractive index and density of the material is known.…”

“…B At constant density, a tissue can acquire a fluid-like state when its cells have small and weak cell-cell contacts (left panel) and a solid-like state when its cells have large, mature and strong cell-cell contacts (right panel). The establishment of the extracellular space and yield stress gradients depends on the function of N-cadherin (Mongera et al, 2018). C A confluent tissue (without interstitial gaps) with cells displaying asymmetric cell shapes and diffusive motion (exemplary trajectories in blue) is in a fluid-like state (left panel), while a confluent tissue consisting of cells with highly symmetric cell shape and caged motion (exemplary trajectories in orange) is in a solid-like state (right panel).…”

“…Moreover, model simulations suggested that the anterior-posterior expansion of the MPZ and PSM can be explained by the maturing PSM exhibiting a rigid state, which can support posterior elongation (Mongera et al, 2018). A potential key player is N-cadherin, since N-cadherin mutant fish display reduced elongation speeds and reduced yield stresses of the PSM (Mongera et al, 2018). A potential key player is N-cadherin, since N-cadherin mutant fish display reduced elongation speeds and reduced yield stresses of the PSM (Mongera et al, 2018).…”

“…Yet, although several molecular components have been suggested to be important for MPZ and PSM elongation, it remains unclear how the above described rheological pattern is determined (Lawton et al, 2013). However, whether N-cadherin is indeed important for determining the rheology of the MPZ and/or PSM is still unclear (Lawton et al, 2013;Serwane et al, 2017;Mongera et al, 2018). However, whether N-cadherin is indeed important for determining the rheology of the MPZ and/or PSM is still unclear (Lawton et al, 2013;Serwane et al, 2017;Mongera et al, 2018).…”